Frontiers in antibiotics最新文献

{"title":"Genomic modifications for enhanced antibiotic production in rifamycin derivative-producing <i>Amycolatopsis mediterranei</i> S699 strains: focusing on <i>rifQ</i> and <i>rifO</i> genes.","authors":"Moritz Müller, Elena Bialas, Irina Sturm, Utkarsh Sood, Rup Lal, Andreas Bechthold","doi":"10.3389/frabi.2024.1399139","DOIUrl":"10.3389/frabi.2024.1399139","url":null,"abstract":"<p><p>Rifamycin and its derivatives are natural products that belong to the class of antibiotic-active polyketides and have significant therapeutic relevance within the therapy scheme of tuberculosis, a worldwide infectious disease caused by <i>Mycobacterium tuberculosis</i>. Improving the oral bioavailability of rifamycin B was achieved through semisynthetic modifications, leading to clinically effective derivatives such as rifampicin. Genetic manipulation of the rifamycin polyketide synthase gene cluster responsible for the production of rifamycin B in the <i>Amycolatopsis mediterranei</i> strain S699 represents a promising tool to generate new rifamycins. These new rifamycins have the potential to be further derivatized into new, ideally more effective, clinically usable compounds. However, the resulting genetically engineered strains only produce these new derivatives in low yields. One example is the strain DCO36, in which <i>rif</i>AT6 was replaced by <i>rap</i>AT2, resulting in the production of rifamycin B and the new derivative 24-desmethyl rifamycin B. Here we describe the successful method adaptation of the PCR-targeting <i>Streptomyces</i> gene replacement approach to <i>Amycolatopsis mediterranei</i> S699 and further on the implementation of genetic modifications that enable an increased production of the derivative 24-desmethyl rifamycin B in the mutant strain DCO36. The described genetic modifications resulted in a mutant strain of DCO36 with <i>rifQ</i> deletion showing a 62% increase in 24-desmethyl rifamycin B production, while a mutant with <i>rifO</i> overexpression showed a 27% increase.</p>","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"3 ","pages":"1399139"},"PeriodicalIF":0.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Antimicrobial resistance in food-producing environments: a One Health approach.","authors":"Getahun E Agga, Kebede Amenu","doi":"10.3389/frabi.2024.1436987","DOIUrl":"10.3389/frabi.2024.1436987","url":null,"abstract":"","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"3 ","pages":"1436987"},"PeriodicalIF":0.0,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A machine learning-based strategy to elucidate the identification of antibiotic resistance in bacteria.","authors":"K T Shreya Parthasarathi, Kiran Bharat Gaikwad, Shruthy Rajesh, Shweta Rana, Akhilesh Pandey, Harpreet Singh, Jyoti Sharma","doi":"10.3389/frabi.2024.1405296","DOIUrl":"10.3389/frabi.2024.1405296","url":null,"abstract":"<p><p>Microorganisms, crucial for environmental equilibrium, could be destructive, resulting in detrimental pathophysiology to the human host. Moreover, with the emergence of antibiotic resistance (ABR), the microbial communities pose the century's largest public health challenges in terms of effective treatment strategies. Furthermore, given the large diversity and number of known bacterial strains, describing treatment choices for infected patients using experimental methodologies is time-consuming. An alternative technique, gaining popularity as sequencing prices fall and technology advances, is to use bacterial genotype rather than phenotype to determine ABR. Complementing machine learning into clinical practice provides a data-driven platform for categorization and interpretation of bacterial datasets. In the present study, k-mers were generated from nucleotide sequences of pathogenic bacteria resistant to antibiotics. Subsequently, they were clustered into groups of bacteria sharing similar genomic features using the Affinity propagation algorithm with a Silhouette coefficient of 0.82. Thereafter, a prediction model based on Random Forest algorithm was developed to explore the prediction capability of the k-mers. It yielded an overall specificity of 0.99 and a sensitivity of 0.98. Additionally, the genes and ABR drivers related to the k-mers were identified to explore their biological relevance. Furthermore, a multilayer perceptron model with a hamming loss of 0.05 was built to classify the bacterial strains into resistant and non-resistant strains against various antibiotics. Segregating pathogenic bacteria based on genomic similarities could be a valuable approach for assessing the severity of diseases caused by new bacterial strains. Utilization of this strategy could aid in enhancing our understanding of ABR patterns, paving the way for more informed and effective treatment options.</p>","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"3 ","pages":"1405296"},"PeriodicalIF":0.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Microbiology: where do we stand?","authors":"Alkiviadis Vatopoulos","doi":"10.3389/frabi.2024.1250632","DOIUrl":"10.3389/frabi.2024.1250632","url":null,"abstract":"<p><p>Clinical Microbiology has developed during the last 100 years, simultaneous with the discovery of microorganisms as causes of infections. Globalization and One Health determine present needs whereas molecular biology, automation, artificial intelligence, and bioinformatics are new tools that characterize the new developments in the field.</p>","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"3 ","pages":"1250632"},"PeriodicalIF":0.0,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic/pharmacodynamic issues for optimizing treatment with beta-lactams of Gram-negative infections in critically ill orthotopic liver transplant recipients: a comprehensive review.","authors":"Milo Gatti, Federico Pea","doi":"10.3389/frabi.2024.1426753","DOIUrl":"10.3389/frabi.2024.1426753","url":null,"abstract":"<p><p>Orthotopic liver transplant (OLT) represents the standard of care for managing patients affected by end-stage and life-threatening liver diseases. Although a significant improvement in surgical techniques, immunosuppressant regimens, and prompt identification of early post-transplant complications resulted in better clinical outcome and survival in OLT recipients, the occurrence of early bacterial infections still represents a remarkable cause of morbidity and mortality. In this scenario, beta-lactams are the most frequent antimicrobials used in critical OLT recipients. The aim of this narrative review was to provide a comprehensive overview of the pathophysiological issues potentially affecting the pharmacokinetics of beta-lactams and to identify potential strategies for maximizing the likelihood of attaining adequate pharmacokinetic/pharmacodynamic (PK/PD) targets of beta-lactams in critically ill OLT recipients. A literature search was carried out on PubMed-MEDLINE database (until 31^st March 2024) in order to retrieve clinical trials, real-world observational evidence, and/or case series/reports evaluating the PK/PD of traditional and novel beta-lactams in settings potentially involving critically ill OLT recipients. Retrieved evidence were categorized according to the concepts of the so-called \"antimicrobial therapy puzzle\", specifically assessing a) beta-lactam PK/PD features, with specific regard to aggressive PK/PD target attainment; b) site of infection, with specific regard to beta-lactam penetration in the lung, ascitic fluid, and bile; and c) pathophysiological alterations, focusing mainly on those specifically associated with OLT. Overall, several research gaps still exist in assessing the PK behavior of beta-lactams in critical OLT recipients. The impact of specific OLT-associated pathophysiological alterations on the attainment of optimal PK/PD targets may represent an important field in which further studies are warranted. Assessing the relationship between aggressive beta-lactam PK/PD target attainment and clinical outcome in critical OLT recipients will represent a major challenge in the next future.</p>","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"3 ","pages":"1426753"},"PeriodicalIF":0.0,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Antibiotics in engineered and natural environments: occurrence, fate, kinetic and microbial impact","authors":"I. Pala-Ozkok, Tugce Katipoglu-Yazan","doi":"10.3389/frabi.2024.1437802","DOIUrl":"https://doi.org/10.3389/frabi.2024.1437802","url":null,"abstract":"","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":" 20","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141372908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Preserving antibiotics: stewardship and effective treatment in low and middle income countries.","authors":"Abdul Ghafur, Stephen H Gillespie","doi":"10.3389/frabi.2024.1432477","DOIUrl":"https://doi.org/10.3389/frabi.2024.1432477","url":null,"abstract":"","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"3 ","pages":"1432477"},"PeriodicalIF":0.0,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased usage of doxycycline for young children with Lyme disease","authors":"Amy D. Thompson, D. Neville, Laura Chapman, F. Balamuth, Meagan M. Ladell, A. Kharbanda, Rachael K. Aresco, L. Nigrovic","doi":"10.3389/frabi.2024.1388039","DOIUrl":"https://doi.org/10.3389/frabi.2024.1388039","url":null,"abstract":"The 2018 Infectious Disease Committee of the American Academy of Pediatrics stated that up to 3 weeks or less of doxycycline is safe in children of all ages. Our goal was to examine trends in doxycycline treatment for children with Lyme disease.We assembled a prospective cohort of children aged 1 to 21 years with Lyme disease who presented to one of eight participating Pedi Lyme Net centers between 2015 and 2023. We defined a Lyme disease case with an erythema migrans (EM) lesion or positive two-tier Lyme disease serology categorized by stage: early-localized (single EM lesion), early-disseminated (multiple EM lesions, cranial neuropathy, meningitis, and carditis), and late (arthritis). We compared doxycycline treatment by age and disease stage and used logistic regression to examine treatment trends.Of the 1,154 children with Lyme disease, 94 (8.1%) had early-localized, 449 (38.9%) had early-disseminated, and 611 (53.0%) had late disease. Doxycycline treatment was more common for older children (83.3% ≥ 8 years vs. 47.1% < 8 years; p < 0.001) and with early-disseminated disease (77.2% early-disseminated vs. 52.1% early-localized or 62.1% late; p < 0.001). For children under 8 years, doxycycline use increased over the study period (6.9% 2015 to 67.9% 2023; odds ratio by year, 1.45; 95% confidence interval, 1.34–1.58).Young children with Lyme disease are frequently treated with doxycycline. Prospective studies are needed to confirm the safety and efficacy of doxycycline in children younger than 8 years, especially for those receiving courses longer than 3 weeks.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"42 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141113688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unguarded liabilities: Borrelia burgdorferi’s complex amino acid dependence exposes unique avenues of inhibition","authors":"Katrina J Holly, Arti Kataria, Daniel P. Flaherty, Ashley M Groshong","doi":"10.3389/frabi.2024.1395425","DOIUrl":"https://doi.org/10.3389/frabi.2024.1395425","url":null,"abstract":"Recent reports from the Centers for Disease Control and Prevention approximate 500,000 cases of Lyme disease in the United States yearly, a significant economic burden on the healthcare system. The standard treatment for Lyme disease includes broad-spectrum antibiotics, which may be administered for extensive periods of time and result in significant impacts to the patient. Recently, we demonstrated that Borrelia burgdorferi, the causative agent of Lyme disease, is uniquely dependent upon peptide acquisition via an oligopeptide transport (Opp) system. This dependence appears unique to the spirochete; thus, the Opp system may constitute a novel and specific target for the inhibition of B. burgdorferi. For proof of concept, we conducted a pilot screen to determine if the Opp system constitutes a viable inhibitor target. OppA2 was utilized as our target protein as it is the most prolific peptide-binding protein throughout the enzootic cycle. We validated a thermal shift assay (TSA) to detect ligand binding against OppA2 and performed a high-throughput screen of 2,240 molecules from a diversity set library. The TSA results identified eight compounds (C1–8) demonstrating potential binding to OppA2, and growth assays identified C2 and C7 as inhibitors of B. burgdorferi growth. We confirmed by TSA that these two compounds interact with additional B. burgdorferi OppAs, potentially resulting in a cumulative inhibitory effect. Additionally, we showed that these compounds have no effect on Escherichia coli, a bacterium that encodes a dispensable Opp system which serves only as an ancillary nutrient transporter. These data demonstrate that the Opp system of B. burgdorferi acts as a viable drug target, with the potential for targeting multiple OppAs with a single compound. Moreover, the lack of inhibition against E. coli suggests that selective targeting of B. burgdorferi via the Opp system may be possible.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"78 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141121238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibiogram profiles of pathogenic and commensal bacteria in goat and sheep feces on smallholder farm","authors":"Ashesh Basnet, Agnes Kilonzo-Nthenge","doi":"10.3389/frabi.2024.1351725","DOIUrl":"https://doi.org/10.3389/frabi.2024.1351725","url":null,"abstract":"The increase of antimicrobial resistance (AMR) in zoonotic pathogens poses a substantial threat to both animal production and human health. Although large-scale animal farms are acknowledged as major reservoirs for AMR, there is a notable knowledge gap concerning AMR in small-scale farms. This study seeks to address this gap by collecting and analyzing 137 fecal samples from goat and sheep farms in Tennessee and Georgia.Bacteria were identified using culture-dependent methods and polymerase chain reaction (PCR), and antimicrobial susceptibility testing (AST) was performed using the Kirby-Bauer Disk Diffusion method.The prevalence of E. coli (94.9%) in goats and sheep significantly exceeded (p < 0.05) that of S. aureus (81.0%), Shigella (35.0%), S. saprophyticus, and Salmonella (3.0%). Salmonella occurrence in goat feces (2.2%) was higher than in sheep (0.8%). Notably, 27% of goats and 8% of sheep tested positive for Shigella spp., while 60% of goats and 21% of sheep tested positive for S. aureus. Antibiotic resistance was observed primarily against ampicillin (79.4%), vancomycin (65.1%), and gentamycin (63.6%), significantly surpassing (p < 0.05) resistance to tetracycline (41.6%) and imipenem (21.8%). The penicillin (79.4%), glycopeptide (65.1%), and aminoglycoside (63.6%) antibiotic classes displayed significantly higher (p < 0.05) resistance compared to tetracyclines (45.7%) and carbapenem (21.8%). Our findings suggest that goats and sheep feces may serve as source for multidrug-resistant bacteria, raising concerns about the potential introduction of their fecal matter into soil, water, and eventually to the food chain. This highlights the need for proactive measures to address and mitigate AMR in goats and sheep within small-scale farms.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"15 23","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140966705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}