Journal Description
Antibiotics
Antibiotics
is an international, peer-reviewed, open access journal on all aspects of antibiotics, published monthly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q1 (Pharmacology & Pharmacy) / CiteScore - Q1 (General Pharmacology, Toxicology and Pharmaceutics)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 13.7 days after submission; acceptance to publication is undertaken in 2.5 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Impact Factor:
4.8 (2022);
5-Year Impact Factor:
4.9 (2022)
Latest Articles
Comparing the Prognostic Impacts of Delayed Administration of Appropriate Antimicrobials in Older Patients with Afebrile and Febrile Community-Onset Bacteremia
Antibiotics 2024, 13(5), 465; https://doi.org/10.3390/antibiotics13050465 (registering DOI) - 19 May 2024
Abstract
Although prompt administration of an appropriate antimicrobial therapy (AAT) is crucial for reducing mortality in the general population with community-onset bacteremia, the prognostic effects of delayed AAT in older individuals with febrile and afebrile bacteremia remain unclear. A stepwise and backward logistic regression
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Although prompt administration of an appropriate antimicrobial therapy (AAT) is crucial for reducing mortality in the general population with community-onset bacteremia, the prognostic effects of delayed AAT in older individuals with febrile and afebrile bacteremia remain unclear. A stepwise and backward logistic regression analysis was used to identify independent predictors of 30-day mortality. In a 7-year multicenter cohort study involving 3424 older patients (≥65 years) with community-onset bacteremia, febrile bacteremia accounted for 27.1% (912 patients). A crucial association of afebrile bacteremia and 30-day mortality (adjusted hazard ratio [AHR], 1.69; p < 0.001) was revealed using Cox regression and Kaplan–Meier curves after adjusting for the independent predictors of mortality. Moreover, each hour of delayed AAT was associated with an average increase of 0.3% (adjusted odds ratio [AOR], 1.003; p < 0.001) and 0.2% (AOR, 1.002; p < 0.001) in the 30-day crude mortality rates among patients with afebrile and febrile bacteremia, respectively, after adjusting for the independent predictors of mortality. Similarly, further analysis based on Cox regression and Kaplan–Meier curves revealed that inappropriate empirical therapy (i.e., delayed AAT administration > 24 h) had a significant prognostic impact, with AHRs of 1.83 (p < 0.001) and 1.76 (p < 0.001) in afebrile and febrile patients, respectively, after adjusting for the independent predictors of mortality. In conclusion, among older individuals with community-onset bacteremia, the dissimilarity of the prognostic impacts of delayed AAT between afebrile and febrile presentation was evident.
Full article
(This article belongs to the Special Issue Successful Antimicrobial Stewardship Approaches to Address Nosocomial Infections)
Open AccessArticle
Whooping Cough Cases Increase in Central Italy after COVID-19 Pandemic
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Giulia Linardos, Luana Coltella, Stefania Ranno, Velia Chiara Di Maio, Luna Colagrossi, Elisabetta Pandolfi, Maria Beatrice Chiarini Testa, Leonardo Genuini, Francesca Stoppa, Matteo Di Nardo, Annalisa Grandin, Renato Cutrera, Corrado Cecchetti, Alberto Villani, Massimiliano Raponi, Paola Bernaschi, Cristina Russo, Carlo Federico Perno and Rossana Scutari
Antibiotics 2024, 13(5), 464; https://doi.org/10.3390/antibiotics13050464 (registering DOI) - 19 May 2024
Abstract
Pertussis continues to be a highly contagious respiratory infection, especially in children, with cyclical peaks of disease spread every three to five years. Here, we report relevant cases of B. pertussis infection between August 2023 and January 2024, and compare them with B.
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Pertussis continues to be a highly contagious respiratory infection, especially in children, with cyclical peaks of disease spread every three to five years. Here, we report relevant cases of B. pertussis infection between August 2023 and January 2024, and compare them with B. pertussis prevalence in pediatric patients admitted to the Reference Italian Pediatric Hospital, located in Rome, from January 2015 to July 2023. A total of 5464 tests for B. pertussis were performed during the study period, and 6.9% were positive. At the time of the COVID-19 pandemic, there was a sharp decrease in the presence of B. pertussis, which reappeared only in August 2023, recording five new cases. All five children presented with paroxysmal cough 5 to 10 days before admission. Four patients had other mild respiratory symptoms and moderate B. pertussis DNA levels (Ct mean: 26). Only one child, with very high B. pertussis DNA levels (Ct: 9), presented with severe respiratory failure. The patients with mild/moderate infection achieved clinical recovery while the patient with the severe manifestation died of cardiac arrest. These observations highlight the reemergence of pertussis even in vaccinated countries and its association with morbidity and mortality especially in young children. This emphasizes the importance of rapid diagnosis to immediately implement appropriate treatment and monitoring of immune status.
Full article
(This article belongs to the Special Issue Epidemiology, Clinical Microbiology and Antimicrobial Therapy: A Shared Effort against Infectious Diseases)
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Open AccessArticle
Risk Factors for Therapeutic Failure and One-Year Mortality in Patients with Intramedullary Nail-Associated Infection after Trochanteric and Subtrochanteric Hip Fracture Repair
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Bernadette Pfang, Marco A. Villegas García, Antonio Blanco García, Álvaro Auñón Rubio, Jaime Esteban and Joaquín García Cañete
Antibiotics 2024, 13(5), 463; https://doi.org/10.3390/antibiotics13050463 (registering DOI) - 18 May 2024
Abstract
Despite the implications of trochanteric and subtrochanteric intramedullary (IM) nail infection for patients with hip fracture, little is known about risk factors for therapeutic failure and mortality in this population. We performed a retrospective observational analysis including patients diagnosed with trochanteric and subtrochanteric
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Despite the implications of trochanteric and subtrochanteric intramedullary (IM) nail infection for patients with hip fracture, little is known about risk factors for therapeutic failure and mortality in this population. We performed a retrospective observational analysis including patients diagnosed with trochanteric and subtrochanteric IM nail infection at a Spanish academic hospital during a 10-year period, with a minimum follow-up of 22 months. Of 4044 trochanteric and subtrochanteric IM nail implants, we identified 35 cases of infection during the study period (0.87%), 17 of which were chronic infections. Patients with therapeutic failure (n = 10) presented a higher average Charlson Comorbidity Index (CCI) (5.40 vs. 4.21, p 0.015, CI 0.26–2.13) and higher rates of polymicrobial (OR 5.70, p 0.033, CI 1.14–28.33) and multidrug-resistant (OR 7.00, p 0.027, CI 1.24–39.57) infections. Upon multivariate analysis, polymicrobial infection and the presence of multidrug-resistant pathogens were identified as independent risk factors for therapeutic failure. Implant retention was associated with an increased risk of failure in chronic infection and was found to be an independent risk factor for overall one-year mortality in the multivariate analysis. Our study highlights the importance of broad-spectrum empirical antibiotics as initial treatment of trochanteric and subtrochanteric IM nail-associated infection while awaiting microbiological results. It also provides initial evidence for the importance of implant removal in chronic IM-nail infection.
Full article
(This article belongs to the Special Issue Antibiotic Therapy in Implant Related Orthopedic Infections)
Open AccessArticle
The Impact of Urinary Catheterization on the Antibiotic Susceptibility of ESBL-Producing Enterobacterales: A Challenging Duo
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Ionela-Larisa Miftode, Andrei Vâță, Radu-Ștefan Miftode, Tudorița Parângă, Mihaela Cătălina Luca, Carmen Manciuc, Amalia Stefana Țimpău, Viorel Radu, Manuel Florin Roșu, Lidia Oana Stămăteanu, Daniela Leca, Dana Teodora Anton-Păduraru and Egidia Gabriela Miftode
Antibiotics 2024, 13(5), 462; https://doi.org/10.3390/antibiotics13050462 - 17 May 2024
Abstract
Introduction: Antimicrobial resistance (AMR) is currently a growing concern among healthcare providers, underscoring the importance of describing the regional susceptibility profile for common microorganisms that are associated with urinary tract infections (UTIs). This knowledge serves as the foundation for proper empirical therapeutic recommendations
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Introduction: Antimicrobial resistance (AMR) is currently a growing concern among healthcare providers, underscoring the importance of describing the regional susceptibility profile for common microorganisms that are associated with urinary tract infections (UTIs). This knowledge serves as the foundation for proper empirical therapeutic recommendations tailored to local susceptibility patterns. Results: We found a high prevalence of ESBL-producing strains (36.9%), with Escherichia coli and Klebsiella spp. being the most prevalent isolated bacteria. Among the catheterized patients, Klebsiella spp. emerged as the primary etiology, with a significant correlation between catheterization and Proteus spp. (p = 0.02) and Providencia stuartii (p < 0.0001). We observed significant correlations between urinary catheterization and older age (68.9 ± 13.7 years vs. 64.2 ± 18.1 years in non-catheterized patients, p = 0.026) and with the presence of an isolate with extensive drug resistance (p < 0.0001) or even pandrug resistance (p < 0.0001). Susceptibility rates significantly decreased for almost all the tested antibiotics during the study period. Notably, susceptibility was markedly lower among catheterized patients, with the most pronounced differences observed for carbapenems (59.6% versus 83.4%, p < 0.0001) and aminoglycosides (37.1% versus 46.9%, p = 0.0001). Materials and Methods: We conducted a retrospective study analyzing the susceptibility profiles of 724 extended-spectrum beta-lactamases (ESBL)-producing Enterobacterales isolated from urine cultures. Our focus was on highlighting susceptibility profiles among isolates associated with urinary catheterization and assessing the shifts in the susceptibility rates over time. Conclusions: The constant rise in AMR rates among Enterobacterales presents significant challenges in treating severe infections, particularly among urinary catheterized patients. This trend leaves clinicians with limited or no effective treatment options. Consequently, the development and implementation of personalized treatment protocols are imperative to ensure efficient empirical therapies.
Full article
(This article belongs to the Special Issue From Detection to Treatment: Navigating Urinary Tract Infections with Antibiotics)
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Open AccessArticle
“Primum, non nocere”: The Epidemiology of Toxigenic Clostridioides difficile Strains in the Antibiotic Era—Insights from a Prospective Study at a Regional Infectious Diseases Hospital in Eastern Europe
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Lidia Oana Stămăteanu, Claudia Elena Pleşca, Ionela Larisa Miftode, Aida Corina Bădescu, Doina Carmen Manciuc, Mihnea Eudoxiu Hurmuzache, Manuel Florin Roșu, Radu Ștefan Miftode, Maria Obreja and Egidia Gabriela Miftode
Antibiotics 2024, 13(5), 461; https://doi.org/10.3390/antibiotics13050461 - 17 May 2024
Abstract
Clostridioides difficile infection (CDI), though identified nearly five decades ago, still remains a major challenge, being associated with significant mortality rates. The strains classified as hypervirulent, notably 027/NAP1/BI, have garnered substantial attention from researchers and clinicians due to their direct correlation with the
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Clostridioides difficile infection (CDI), though identified nearly five decades ago, still remains a major challenge, being associated with significant mortality rates. The strains classified as hypervirulent, notably 027/NAP1/BI, have garnered substantial attention from researchers and clinicians due to their direct correlation with the severity of the disease. Our study aims to elucidate the significance of toxigenic Clostridioides difficile (CD) strains in the clinical and therapeutic aspects of managing patients diagnosed with CDI. We conducted a single-center prospective study, including patients with CDI from north-eastern Romania. We subsequently conducted molecular biology testing to ascertain the prevalence of the presumptive 027/NAP1/BI strain within aforementioned geographic region. The patients were systematically compared and assessed both clinically and biologically, employing standardized and comparative methodologies. The study enrolled fifty patients with CDI admitted between January 2020 and June 2020. Among the investigated patients, 43 (86%) exhibited infection with toxigenic CD strains positive for toxin B genes (tcdB), binary toxin genes (cdtA and cdtB), and deletion 117 in regulatory genes (tcdC), while the remaining 7 (14%) tested negative for binary toxin genes (cdtA and cdtB) and deletion 117 in tcdC. The presence of the presumptive 027/NAP1/BI strains was linked to a higher recurrence rate (35.56%, p = 0.025), cardiovascular comorbidities (65.1% vs. 14.2%, p = 0.016), and vancomycin treatment (55.8% vs. 14.3%, p = 0.049). The findings of our investigation revealed an elevated incidence of colitis attributed to presumptive 027/NAP1/BI. Despite the prevalence of the presumptive 027 strain and its associated heightened inflammation among the patients studied, no significant differences were observed regarding the clinical course or mortality outcomes.
Full article
(This article belongs to the Special Issue Bacterial-Associated Infections: Epidemiology, Antimicrobial Resistance and Its Impact on Health)
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Open AccessBrief Report
Rational Antibiotic Prescribing Is Underpinned by Dental Ethics Principles: Survey on Postgraduate and Undergraduate Dental Students’ Perceptions
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Jelena Roganović and Milena Barać
Antibiotics 2024, 13(5), 460; https://doi.org/10.3390/antibiotics13050460 - 17 May 2024
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Background: Dentists bear the burden of responsibility for antimicrobial resistance since antibiotics are the drugs most prescribed by dentists. Often, “inappropriate” antibiotic use is considered as a “gray area” by dentists mainly due to ethical challenges associated with the clinical judgement depending on
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Background: Dentists bear the burden of responsibility for antimicrobial resistance since antibiotics are the drugs most prescribed by dentists. Often, “inappropriate” antibiotic use is considered as a “gray area” by dentists mainly due to ethical challenges associated with the clinical judgement depending on patients and/or prescribers. Aim: The study aimed to assess whether and in what way dental ethical principles underpin rational antibiotic use by investigating perceptions of postgraduate and undergraduate dental students without formal knowledge of dental ethics. Method: A cross-sectional anonymous survey comprised nine close-ended questions and was conducted among dental students (n = 125). The investigated practice of appropriate antibiotic prescribing in the survey relied on the respect of three basic principles of ethics: autonomy, non-maleficence, and beneficence. Results: Results show that dental students exhibit a lack of dental ethics knowledge that results in an inappropriate antibiotic-prescribing practice: prescribing an antibiotic when it is not necessary, without examination, or for indications that are not within the competence of the dentist. Multivariate regression analysis revealed that there was a significant difference between under- and postgraduates. Conclusions: Within the pharmacology course, a review of the clinical scenarios which cover both ethical and clinical complexities regarding the appropriate use of antibiotics should be introduced as an educational approach.
Full article
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Open AccessArticle
Genomic Analysis of Kitasatospora setae to Explore Its Biosynthetic Potential Regarding Secondary Metabolites
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Yutong Xue, Zhiyan Zhou, Fangjian Feng, Hang Zhao, Shuangling Tan, Jinling Li, Sitong Wu, Zhiran Ju, Shan He and Lijian Ding
Antibiotics 2024, 13(5), 459; https://doi.org/10.3390/antibiotics13050459 - 16 May 2024
Abstract
Actinomycetes have long been recognized as important sources of clinical antibiotics. However, the exploration of rare actinomycetes, despite their potential for producing bioactive molecules, has remained relatively limited compared to the extensively studied Streptomyces genus. The extensive investigation of Streptomyces species and their
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Actinomycetes have long been recognized as important sources of clinical antibiotics. However, the exploration of rare actinomycetes, despite their potential for producing bioactive molecules, has remained relatively limited compared to the extensively studied Streptomyces genus. The extensive investigation of Streptomyces species and their natural products has led to a diminished probability of discovering novel bioactive compounds from this group. Consequently, our research focus has shifted towards less explored actinomycetes, beyond Streptomyces, with particular emphasis on Kitasatospora setae (K. setae). The genome of K. setae was annotated and analyzed through whole-genome sequencing using multiple bio-informatics tools, revealing an 8.6 Mbp genome with a 74.42% G+C content. AntiSMASH analysis identified 40 putative biosynthetic gene clusters (BGCs), approximately half of which were recessive and unknown. Additionally, metabolomic mining utilizing mass spectrometry demonstrated the potential for this rare actinomycete to generate numerous bioactive compounds such as glycosides and macrolides, with bafilomycin being the major compound produced. Collectively, genomics- and metabolomics-based techniques confirmed K. setae’s potential as a bioactive secondary metabolite producer that is worthy of further exploration.
Full article
Open AccessArticle
Detection of Salmonella Pathogenicity Islands and Antimicrobial-Resistant Genes in Salmonella enterica Serovars Enteritidis and Typhimurium Isolated from Broiler Chickens
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Tsepo Ramatla, Ntelekwane G. Khasapane, Lungile N. Mlangeni, Prudent Mokgokong, Taole Ramaili, Rendani Ndou, Jane S. Nkhebenyane, Kgaugelo Lekota and Oriel Thekisoe
Antibiotics 2024, 13(5), 458; https://doi.org/10.3390/antibiotics13050458 - 16 May 2024
Abstract
Rapid growth in commercial poultry production is one of the major sources of Salmonella infections that leads to human salmonellosis. The two main Salmonella enterica serovars associated with human salmonellosis are enteritidis and typhimurium. The aim of this study was to determine the
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Rapid growth in commercial poultry production is one of the major sources of Salmonella infections that leads to human salmonellosis. The two main Salmonella enterica serovars associated with human salmonellosis are enteritidis and typhimurium. The aim of this study was to determine the prevalence of S. enterica serovars Enteritidis and S. Typhimurium as well as their Salmonella pathogenicity islands (SPI) and antibiotic resistance profiles in broiler chicken feces from slaughterhouses. A total of 480 fecal samples from broiler chickens that were grouped into 96 pooled samples were identified to have Salmonella spp. using the invA gene, whilst the Spy and sdfI genes were used to screen for the presence of S. Enteritidis and S. Typhimurium serovars, respectively, by polymerase chain reaction (PCR) assays. The isolates were also screened for the presence of Salmonella pathogenicity islands (SPIs) using PCR. The disc diffusion assay was performed to determine the antibiotic resistance profiles of the isolates. A total of 36 isolates were confirmed as Salmonella spp. through amplification of the invA gene. Out of 36 confirmed Salmonella spp. a total of 22 isolates were classified as S. Enteritidis (n = 8) and were S. Typhimurium (n = 14) serovars. All (n = 22) S. Enteritidis and S. Typhimurium isolates possessed the hilA (SPI-1), ssrB (SPI-2) and pagC (SPI-11) pathogenicity islands genes. Amongst these serovars, 50% of the isolates (n = 11/22) were resistant to tetracycline and nalidixic acid. Only 22% of the isolates, S. Typhimurium (13.6%) and S. Enteritidis (9.1%) demonstrated resistance against three or more antibiotic classes. The most detected antibiotic resistance genes were tet(K), mcr-1, sulI and strA with 13 (59.1%), 9 (40.9%), 9 (40.9%) and 7 (31.8%), respectively. The findings of this study revealed that S. Typhimurium is the most prevalent serotype detected in chicken feces. To reduce the risk to human health posed by salmonellosis, a stringent public health and food safety policy is required.
Full article
(This article belongs to the Special Issue Antimicrobial Resistance and Infections in Veterinary Settings)
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Open AccessReview
Pharmacovigilance Strategies to Address Resistance to Antibiotics and Inappropriate Use—A Narrative Review
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Valcieny Sandes, Albert Figueras and Elisangela Costa Lima
Antibiotics 2024, 13(5), 457; https://doi.org/10.3390/antibiotics13050457 - 16 May 2024
Abstract
The spread of antimicrobial resistance (AMR) is a global challenge. Close and continuous surveillance for quick detection of AMR can be difficult, especially in remote places. This narrative review focuses on the contributions of pharmacovigilance (PV) as an auxiliary tool for identifying and
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The spread of antimicrobial resistance (AMR) is a global challenge. Close and continuous surveillance for quick detection of AMR can be difficult, especially in remote places. This narrative review focuses on the contributions of pharmacovigilance (PV) as an auxiliary tool for identifying and monitoring the ineffectiveness, resistance, and inappropriate use of antibiotics (ABs). The terms “drug ineffective”, “therapeutic failure”, “drug resistance”, “pathogen resistance”, and “multidrug resistance” were found in PV databases and dictionaries, denoting ineffectiveness. These terms cover a range of problems that should be better investigated because they are useful in warning about possible causes of AMR. “Medication errors”, especially those related to dose and indication, and “Off-label use” are highlighted in the literature, suggesting inappropriate use of ABs. Hence, the included studies show that the terms of interest related to AMR and use are not only present but frequent in PV surveillance programs. This review illustrates the feasibility of using PV as a complementary tool for antimicrobial stewardship activities, especially in scenarios where other resources are scarce.
Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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Open AccessArticle
Dissemination of Ceftriaxone-Resistant Salmonella Enteritidis Harboring Plasmids Encoding blaCTX-M-55 or blaCTX-M-14 Gene in China
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Siyuan Yang, Jianzhong Fan, Lifei Yu, Jintao He, Linghong Zhang, Yunsong Yu and Xiaoting Hua
Antibiotics 2024, 13(5), 456; https://doi.org/10.3390/antibiotics13050456 - 16 May 2024
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Salmonella Enteritidis was the primary foodborne pathogen responsible for acute gastroenteritis. The growing ceftriaxone resistance poses a significant threat to public health. Infection with S. Enteritidis has emerged as a major public health concern, particularly in developing countries. However, research on ceftriaxone-resistant S.
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Salmonella Enteritidis was the primary foodborne pathogen responsible for acute gastroenteritis. The growing ceftriaxone resistance poses a significant threat to public health. Infection with S. Enteritidis has emerged as a major public health concern, particularly in developing countries. However, research on ceftriaxone-resistant S. Enteritidis (CRO-RSE) remains limited, particularly concerning its resistance mechanism, plasmid structure, and transmission characteristics. This study aims to address these gaps comprehensively. We collected 235 S. Enteritidis isolates from Hangzhou First People’s Hospital between 2010 and 2020. Among these, 8.51% (20/235) exhibited resistance to ceftriaxone. Whole-genome analysis revealed that 20 CRO-RSE isolates harbored blaCTX-M-55 or blaCTX-M-14 on the plasmid. Moreover, the dissemination of the blaCTX-M-type gene was associated with IS26 and ISEcp1. Plasmid fusion entailing the integration of the p1 plasmid with antibiotic resistance genes and the p2 (pSEV) virulence plasmid was observed in certain CRO-RSE. Additionally, the structural analysis of the plasmids unveiled two types carrying the blaCTX-M-type gene: type A with multiple replicons and type B with IncI1 (Alpha) replicon. Type B plasmids exhibited superior adaptability and stability compared to type A plasmids within Enterobacteriaceae. Interestingly, although the type B (S808-p1) plasmid displayed the potential to spread to Acinetobacter baumannii, it failed to maintain stability in this species.
Full article
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Open AccessArticle
Genomic Characterization of Carbapenemase-Producing Enterobacter hormaechei, Serratia marcescens, Citrobacter freundii, Providencia stuartii, and Morganella morganii Clinical Isolates from Bulgaria
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Stefana Sabtcheva, Ivan Stoikov, Ivan N. Ivanov, Deyan Donchev, Magdalena Lesseva, Sylvia Georgieva, Deana Teneva, Elina Dobreva and Iva Christova
Antibiotics 2024, 13(5), 455; https://doi.org/10.3390/antibiotics13050455 - 16 May 2024
Abstract
Carbapenemase-producing Enterobacter spp. Serratia marcescens, Citrobacter freundii, Providencia spp., and Morganella morganii (CP-ESCPM) are increasingly identified as causative agents of nosocomial infections but are still not under systematic genomic surveillance. In this study, using a combination of whole-genome sequencing and conjugation
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Carbapenemase-producing Enterobacter spp. Serratia marcescens, Citrobacter freundii, Providencia spp., and Morganella morganii (CP-ESCPM) are increasingly identified as causative agents of nosocomial infections but are still not under systematic genomic surveillance. In this study, using a combination of whole-genome sequencing and conjugation experiments, we sought to elucidate the genomic characteristics and transferability of resistance genes in clinical CP-ESCPM isolates from Bulgaria. Among the 36 sequenced isolates, NDM-1 (12/36), VIM-4 (11/36), VIM-86 (8/36), and OXA-48 (7/36) carbapenemases were identified; two isolates carried both NDM-1 and VIM-86. The majority of carbapenemase genes were found on self-conjugative plasmids. IncL plasmids were responsible for the spread of OXA-48 among E. hormaechei, C. freundii, and S. marcescens. IncM2 plasmids were generally associated with the spread of NDM-1 in C. freundii and S. marcescens, and also of VIM-4 in C. freundii. IncC plasmids were involved in the spread of the recently described VIM-86 in P. stuartii isolates. IncC plasmids carrying blaNDM-1 and blaVIM-86 were observed too. blaNDM-1 was also detected on IncX3 in S. marcescens and on IncT plasmid in M. morganii. The significant resistance transfer rates we observed highlight the role of the ESCPM group as a reservoir of resistance determinants and stress the need for strengthening infection control measures.
Full article
(This article belongs to the Special Issue The Evolution of Plasmid-Mediated Antimicrobial Resistance)
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Open AccessArticle
Rumi and Pasteurized Kareish Cheeses Are a Source of β-Lactam-Resistant Salmonella in the Nile Delta Region of Egypt: Insights into Their Incidence, AMR Pattern, Genotypic Determinants of Virulence and β-Lactam Resistance
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Fatma Elzhraa, Maha Al-Ashmawy, Mohammed El-Sherbini, Ahmed M. El-Sebaey, Csilla Mohácsi-Farkas, Gabriella Kiskó and Ágnes Belák
Antibiotics 2024, 13(5), 454; https://doi.org/10.3390/antibiotics13050454 - 16 May 2024
Abstract
The spread of superbugs in dairy products can jeopardize global public health. To date, information on the incidence rates of virulent and β-lactams-resistant (BLR) Salmonella in cheeses from rural areas of Egypt has been lacking. Biochemical, serological, antibiotic susceptibility, and multiplex PCR (M-PCR)
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The spread of superbugs in dairy products can jeopardize global public health. To date, information on the incidence rates of virulent and β-lactams-resistant (BLR) Salmonella in cheeses from rural areas of Egypt has been lacking. Biochemical, serological, antibiotic susceptibility, and multiplex PCR (M-PCR) tests were performed to identify and characterize Salmonella isolates. In this study, 44 (15.71%) Salmonella isolates of eight different serotypes were recovered from 280 samples of Rumi and pasteurized Kariesh cheeses across the Nile Delta region of Egypt. The most predominant serotypes were S. Typhimurium, S. Enteritidis, and S. Infantis. The virulence genes (invA, stn, and hilA) were identified in all isolates. However, spvC was only detected in S. Typhimurium. The highest resistance was developed against Erythromycin and Clindamycin (90.91%), followed by Ceftazidime and Cephalothin (84.09%). Meropenem and colistin were the most effective antibiotics. A high proportion (79.55%) of multi-drug resistance (MDR) isolates carried narrow spectrum (NS), extended-spectrum (ES), and AmpC-BLR genes. The blaOXA-1, blaOXA-2, blaTEM-1, blaCTX-M, blaCMY-1, and blaCMY-2 BLR genes were positive in 37.04%, 29.63%, 25.93%, 14.81%, 37.04%, and 3.70% of isolates, respectively. In conclusion, a high prevalence of virulence and BLR genes harboring Salmonella strains in Egyptian cheeses is considered a great threat to public health.
Full article
(This article belongs to the Special Issue Research of Antimicrobial Resistance in the Food Chain)
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Open AccessArticle
Role of Cefiderocol in Multidrug-Resistant Gram-Negative Central Nervous System Infections: Real Life Experience and State-of-the-Art
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Alessio Sollima, Francesco Rossini, Paola Lanza, Carlo Pallotto, Marianna Meschiari, Ivan Gentile, Roberto Stellini, Angelica Lenzi, Alice Mulé, Francesca Castagna, Silvia Lorenzotti, Silvia Amadasi, Evelyn Van Hauwermeiren, Barbara Saccani, Benedetta Fumarola, Liana Signorini, Francesco Castelli and Alberto Matteelli
Antibiotics 2024, 13(5), 453; https://doi.org/10.3390/antibiotics13050453 - 16 May 2024
Abstract
Cefiderocol is a new molecule effective against multidrug-resistant (MDR) Gram-negative pathogens. Currently, there is limited evidence regarding the use of cefiderocol in central nervous system (CNS) infections. Data on the cerebrospinal fluid penetration rate of cefiderocol are limited and heterogeneous, and there is
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Cefiderocol is a new molecule effective against multidrug-resistant (MDR) Gram-negative pathogens. Currently, there is limited evidence regarding the use of cefiderocol in central nervous system (CNS) infections. Data on the cerebrospinal fluid penetration rate of cefiderocol are limited and heterogeneous, and there is no consensus on the dosing scheme of cefiderocol to penetrate the blood–brain barrier. We present a case series and a literature review of CNS infections caused by MDR pathogens that were treated with cefiderocol: some of these patients were treated with different dose schemes of cefiderocol and underwent therapeutic drug monitoring both on plasma and cerebrospinal fluid (CSF). The CSF penetration rates and the clinical outcomes were evaluated.
Full article
(This article belongs to the Special Issue Antimicrobial Treatment and Management of Central Nervous System Infections)
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Open AccessArticle
Genetic Alternatives for Experimental Adaptation to Colistin in Three Pseudomonas aeruginosa Lineages
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Igor Chebotar, Tatiana Savinova, Julia Bocharova, Dmitriy Korostin, Peter Evseev and Nikolay Mayanskiy
Antibiotics 2024, 13(5), 452; https://doi.org/10.3390/antibiotics13050452 - 15 May 2024
Abstract
Pseudomonas aeruginosa is characterized by a high adaptive potential, developing resistance in response to antimicrobial pressure. We employed a spatiotemporal evolution model to disclose the pathways of adaptation to colistin, a last-resort polymyxin antimicrobial, among three unrelated P. aeruginosa lineages. The P. aeruginosa
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Pseudomonas aeruginosa is characterized by a high adaptive potential, developing resistance in response to antimicrobial pressure. We employed a spatiotemporal evolution model to disclose the pathways of adaptation to colistin, a last-resort polymyxin antimicrobial, among three unrelated P. aeruginosa lineages. The P. aeruginosa ATCC-27833 reference strain (Pa_ATCC), an environmental P. aeruginosa isolate (Pa_Environment), and a clinical isolate with multiple drug resistance (Pa_MDR) were grown over an increasing 5-step colistin concentration gradient from 0 to 400 mg/L. Pa_Environment demonstrated the highest growth pace, achieving the 400 mg/L band in 15 days, whereas it took 37 and 60 days for Pa_MDR and Pa_ATCC, respectively. To identify the genome changes that occurred during adaptation to colistin, the isolates selected during the growth of the bacteria (n = 185) were subjected to whole genome sequencing. In total, 17 mutation variants in eight lipopolysaccharide-synthesis-associated genes were detected. phoQ and lpxL/PA0011 were affected in all three lineages, whereas changes in pmrB were found in Pa_Environment and Pa_MDR but not in Pa_ATCC. In addition, mutations were detected in 34 general metabolism genes, and each lineage developed mutations in a unique set of such genes. Thus, the three examined distinct P. aeruginosa strains demonstrated different capabilities and genetic pathways of colistin adaptation.
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Open AccessArticle
Eminent Antimicrobial Peptide Resistance in Zymomonas mobilis: A Novel Advantage of Intrinsically Uncoupled Energetics
by
Reinis Rutkis, Zane Lasa, Marta Rubina, Inese Strazdina and Uldis Kalnenieks
Antibiotics 2024, 13(5), 451; https://doi.org/10.3390/antibiotics13050451 - 15 May 2024
Abstract
Relative to several model bacteria, the ethanologenic bacterium Zymomonas mobilis is shown here to have elevated resistance to exogenous antimicrobial peptides (AMPs)—with regard to both peptide bulk concentration in the medium and the numbers of peptide molecules per cell. By monitoring the integration
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Relative to several model bacteria, the ethanologenic bacterium Zymomonas mobilis is shown here to have elevated resistance to exogenous antimicrobial peptides (AMPs)—with regard to both peptide bulk concentration in the medium and the numbers of peptide molecules per cell. By monitoring the integration of AMPs in the bacterial cell membrane and observing the resulting effect on membrane energy coupling, it is concluded that the membranotropic effects of the tested AMPs in Z. mobilis and in Escherichia coli are comparable. The advantage of Z. mobilis over E. coli apparently results from its uncoupled mode of energy metabolism that, in contrast to E. coli, does not rely on oxidative phosphorylation, and hence, is less vulnerable to the disruption of its energy-coupling membrane by AMPs. It is concluded that the high resistance to antimicrobial peptides (AMPs) observed in Z. mobilis not only proves crucial for its survival in its natural environment but also offers a promising platform for AMP production and sheds light on potential strategies for novel resistance development in clinical settings.
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(This article belongs to the Section Antimicrobial Peptides)
Open AccessArticle
Potential Surviving Effect of Cleome droserifolia Extract against Systemic Staphylococcus aureus Infection: Investigation of the Chemical Content of the Plant
by
Jawaher Alqahtani, Walaa A. Negm, Engy Elekhnawy, Ismail A. Hussein, Hassan Samy Hassan, Abdullah R. Alanzi, Ehssan Moglad, Rehab Ahmed, Sarah Ibrahim and Suzy A. El-Sherbeni
Antibiotics 2024, 13(5), 450; https://doi.org/10.3390/antibiotics13050450 - 15 May 2024
Abstract
The increasing rates of morbidity and mortality owing to bacterial infections, particularly Staphylococcus aureus have necessitated finding solutions to face this issue. Thus, we elucidated the phytochemical constituents and antibacterial potential of Cleome droserifolia extract (CDE). Using LC-ESI-MS/MS, the main phytoconstituents of CDE
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The increasing rates of morbidity and mortality owing to bacterial infections, particularly Staphylococcus aureus have necessitated finding solutions to face this issue. Thus, we elucidated the phytochemical constituents and antibacterial potential of Cleome droserifolia extract (CDE). Using LC-ESI-MS/MS, the main phytoconstituents of CDE were explored, which were kaempferol-3,7-O-bis-alpha-L-rhamnoside, isorhamnetin, cyanidin-3-glucoside, kaempferide, kaempferol-3-O-alpha-L-rhamnoside, caffeic acid, isoquercitrin, quinic acid, isocitrate, mannitol, apigenin, acacetin, and naringenin. The CDE exerted an antibacterial action on S. aureus isolates with minimum inhibitory concentrations ranging from 128 to 512 µg/mL. Also, CDE exhibited antibiofilm action using a crystal violet assay. A scanning electron microscope was employed to illuminate the effect of CDE on biofilm formation, and it considerably diminished S. aureus cell number in the biofilm. Moreover, qRT-PCR was performed to study the effect of CDE on biofilm gene expression (cna, fnbA, and icaA). The CDE revealed a downregulating effect on the studied biofilm genes in 43.48% of S. aureus isolates. Regarding the in vivo model, CDE significantly decreased the S. aureus burden in the liver and spleen of CDE-treated mice. Also, it significantly improved the mice’s survival and substantially decreased the inflammatory markers (interleukin one beta and interleukin six) in the studied tissues. Furthermore, CDE has improved the histology and tumor necrosis factor alpha immunohistochemistry in the liver and spleen of the CDE-treated group. Thus, CDE could be considered a promising candidate for future antimicrobial drug discovery studies.
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(This article belongs to the Special Issue Antibacterial, Antibiofilm and Anti-virulence Activity Research of Both Natural and Synthetic Products, 2nd Edition)
Open AccessArticle
The Tick Saliva Peptide HIDfsin2 TLR4-Dependently Inhibits the Tick-Borne Severe Fever with Thrombocytopenia Syndrome Virus in Mouse Macrophages
by
Luyao Wang, Yishuo Liu, Rui Pang, Yiyuan Guo, Yingying Ren, Yingliang Wu and Zhijian Cao
Antibiotics 2024, 13(5), 449; https://doi.org/10.3390/antibiotics13050449 - 15 May 2024
Abstract
Ticks transmit a variety of pathogens to their hosts by feeding on blood. The interactions and struggle between tick pathogens and hosts have evolved bilaterally. The components of tick saliva can directly or indirectly trigger host biological responses in a manner that promotes
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Ticks transmit a variety of pathogens to their hosts by feeding on blood. The interactions and struggle between tick pathogens and hosts have evolved bilaterally. The components of tick saliva can directly or indirectly trigger host biological responses in a manner that promotes pathogen transmission; however, host cells continuously develop strategies to combat pathogen infection and transmission. Moreover, it is still unknown how host cells develop their defense strategies against tick-borne viruses during tick sucking. Here, we found that the tick saliva peptide HIDfsin2 enhanced the antiviral innate immunity of mouse macrophages by activating the Toll-like receptor 4 (TLR4) signaling pathway, thereby restricting tick-borne severe fever with thrombocytopenia syndrome virus (SFTSV) replication. HIDfsin2 was identified to interact with lipopolysaccharide (LPS), a ligand of TLR4, and then depolymerize LPS micelles into smaller particles, effectively enhancing the activation of the nuclear factor kappa-B (NF-κB) and type I interferon (IFN-I) signaling pathways, which are downstream of TLR4. Expectedly, TLR4 knockout completely eliminated the promotion effect of HIDfsin2 on NF-κB and type I interferon activation. Moreover, HIDfsin2 enhanced SFTSV replication in TLR4-knockout mouse macrophages, which is consistent with our recent report that HIDfsin2 hijacked p38 mitogen-activated protein kinase (MAPK) to promote the replication of tick-borne SFTSV in A549 and Huh7 cells (human cell lines) with low expression of TLR4. Together, these results provide new insights into the innate immune mechanism of host cells following tick bites. Our study also shows a rare molecular event relating to the mutual antagonism between tick-borne SFTSV and host cells mediated by the tick saliva peptide HIDfsin2 at the tick–host–virus interface.
Full article
(This article belongs to the Special Issue Peptide Antibiotics from Microbes and Venomous Animals, 2nd Edition)
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Open AccessArticle
Colonization by Extended-Spectrum β-Lactamase-Producing Enterobacterales and Bacteremia in Hematopoietic Stem Cell Transplant Recipients
by
Luiza Arcas Gonçalves, Beatriz Barbosa Anjos, Bruno Melo Tavares, Ana Paula Marchi, Marina Farrel Côrtes, Hermes Ryoiti Higashino, Bruna del Guerra de Carvalho Moraes, José Victor Bortolotto Bampi, Liliane Dantas Pinheiro, Fernanda de Souza Spadao, Vanderson Rocha, Thais Guimarães and Silvia Figueiredo Costa
Antibiotics 2024, 13(5), 448; https://doi.org/10.3390/antibiotics13050448 - 15 May 2024
Abstract
Background: Assessing the risk of multidrug-resistant colonization and infections is pivotal for optimizing empirical therapy in hematopoietic stem cell transplants (HSCTs). Limited data exist on extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) colonization in this population. This study aimed to assess whether ESBL-E colonization constitutes a
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Background: Assessing the risk of multidrug-resistant colonization and infections is pivotal for optimizing empirical therapy in hematopoietic stem cell transplants (HSCTs). Limited data exist on extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) colonization in this population. This study aimed to assess whether ESBL-E colonization constitutes a risk factor for ESBL-E bloodstream infection (BSI) and to evaluate ESBL-E colonization in HSCT recipients. Methods: A retrospective analysis of ESBL-E colonization and BSI in HSCT patients was conducted from August 2019 to June 2022. Weekly swabs were collected and cultured on chromogenic selective media, with PCR identifying the β-lactamase genes. Pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS) assessed the colonizing strains’ similarities. Results: Of 222 evaluated HSCT patients, 59.45% were colonized by ESBL-E, with 48.4% at admission. The predominant β-lactamase genes were blaTEM (52%) and blaSHV (20%). PFGE analysis did not reveal predominant clusters in 26 E. coli and 15 K. pneumoniae strains. WGS identified ST16 and ST11 as the predominant sequence types among K. pneumoniae. Thirty-three patients developed thirty-five Enterobacterales-BSIs, with nine being third-generation cephalosporin-resistant. No association was found between ESBL-E colonization and ESBL-BSI (p = 0.087). Conclusions: Although the patients presented a high colonization rate of ESBL-E upon admission, no association between colonization and infection were found. Thus, it seems that ESBL screening is not a useful strategy to assess risk factors and guide therapy for ESBL-BSI in HSCT-patients.
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(This article belongs to the Special Issue Colonization and Infection of Multi-Drug Resistant Organisms)
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Open AccessArticle
Listeria monocytogenes from Food Products and Food Associated Environments: Antimicrobial Resistance, Genetic Clustering and Biofilm Insights
by
Adriana Silva, Vanessa Silva, João Paulo Gomes, Anabela Coelho, Rita Batista, Cristina Saraiva, Alexandra Esteves, Ângela Martins, Diogo Contente, Lara Diaz-Formoso, Luis M. Cintas, Gilberto Igrejas, Vítor Borges and Patrícia Poeta
Antibiotics 2024, 13(5), 447; https://doi.org/10.3390/antibiotics13050447 - 14 May 2024
Abstract
Listeria monocytogenes, a foodborne pathogen, exhibits high adaptability to adverse environmental conditions and is common in the food industry, especially in ready-to-eat foods. L. monocytogenes strains pose food safety challenges due to their ability to form biofilms, increased resistance to disinfectants, and
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Listeria monocytogenes, a foodborne pathogen, exhibits high adaptability to adverse environmental conditions and is common in the food industry, especially in ready-to-eat foods. L. monocytogenes strains pose food safety challenges due to their ability to form biofilms, increased resistance to disinfectants, and long-term persistence in the environment. The aim of this study was to evaluate the presence and genetic diversity of L. monocytogenes in food and related environmental products collected from 2014 to 2022 and assess antibiotic susceptibility and biofilm formation abilities. L. monocytogenes was identified in 13 out of the 227 (6%) of samples, 7 from food products (meat preparation, cheeses, and raw milk) and 6 from food-processing environments (slaughterhouse-floor and catering establishments). All isolates exhibited high biofilm-forming capacity and antibiotic susceptibility testing showed resistance to several classes of antibiotics, especially trimethoprim-sulfamethoxazole and erythromycin. Genotyping and core-genome clustering identified eight sequence types and a cluster of three very closely related ST3 isolates (all from food), suggesting a common contamination source. Whole-genome sequencing (WGS) analysis revealed resistance genes conferring resistance to fosfomycin (fosX), lincosamides (lin), fluoroquinolones (norB), and tetracycline (tetM). In addition, the qacJ gene was also detected, conferring resistance to disinfecting agents and antiseptics. Virulence gene profiling revealed the presence of 92 associated genes associated with pathogenicity, adherence, and persistence. These findings underscore the presence of L. monocytogenes strains in food products and food-associated environments, demonstrating a high virulence of these strains associated with resistance genes to antibiotics, but also to disinfectants and antiseptics. Moreover, they emphasize the need for continuous surveillance, effective risk assessment, and rigorous control measures to minimize the public health risks associated to severe infections, particularly listeriosis outbreaks. A better understanding of the complex dynamics of pathogens in food products and their associated environments can help improve overall food safety and develop more effective strategies to prevent severe health consequences and economic losses.
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(This article belongs to the Special Issue Rise of Antibiotic Resistance: Mechanisms Involved and Solutions to Tackle It)
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Characterization of Salmonella Phage P1-CTX and the Potential Mechanism Underlying the Acquisition of the blaCTX-M-27 Gene
by
Qiu-Yun Zhao, Run-Mao Cai, Ping Cai, Lin Zhang, Hong-Xia Jiang and Zhen-Ling Zeng
Antibiotics 2024, 13(5), 446; https://doi.org/10.3390/antibiotics13050446 - 14 May 2024
Abstract
The P1 phage has garnered attention as a carrier of antibiotic resistance genes (ARGs) in Enterobacteriaceae. However, the transferability of ARGs by P1-like phages carrying ARGs, in addition to the mechanism underlying ARG acquisition, remain largely unknown. In this study, we elucidated the
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The P1 phage has garnered attention as a carrier of antibiotic resistance genes (ARGs) in Enterobacteriaceae. However, the transferability of ARGs by P1-like phages carrying ARGs, in addition to the mechanism underlying ARG acquisition, remain largely unknown. In this study, we elucidated the biological characteristics, the induction and transmission abilities, and the acquisition mechanism of the blaCTX-M-27 gene in the P1 phage. The P1-CTX phage exhibited distinct lytic plaques and possessed a complete head and tail structure. Additionally, the P1-CTX phage was induced successfully under various conditions, including UV exposure, heat treatment at 42 °C, and subinhibitory concentrations (sub-MICs) of antibiotics. Moreover, the P1-CTX phage could mobilize the blaCTX-M-27 gene into three strains of Escherichia coli (E. coli) and the following seven different serotypes of Salmonella: Rissen, Derby, Kentucky, Typhimurium, Cerro, Senftenberg, and Muenster. The mechanism underlying ARG acquisition by the P1-CTX phage involved Tn1721 transposition-mediated movement of blaCTX-M-27 into the ref and mat genes within its genome. To our knowledge, this is the first report documenting the dynamic processes of ARG acquisition by a phage. Furthermore, this study enriches the research on the mechanism underlying the phage acquisition of drug resistance genes and provides a basis for determining the risk of drug resistance during phage transmission.
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(This article belongs to the Special Issue Antibiotic Residues, Antimicrobial Resistance and Intervention Strategies of Foodborne Pathogens, 2nd Edition)
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