Antibiotics-BaselPub Date : 2024-12-04DOI: 10.3390/antibiotics13121173
Meryl Cinzía Tila Tamara Gramberg, Bart Torensma, Suzanne van Asten, Elske Sieswerda, Louise Willy Elizabeth Sabelis, Martin den Heijer, Ralph de Vries, Vincent de Groot, Edgar Josephus Gerardus Peters
{"title":"Duration of Antibiotic Treatment for Foot Osteomyelitis in People with Diabetes.","authors":"Meryl Cinzía Tila Tamara Gramberg, Bart Torensma, Suzanne van Asten, Elske Sieswerda, Louise Willy Elizabeth Sabelis, Martin den Heijer, Ralph de Vries, Vincent de Groot, Edgar Josephus Gerardus Peters","doi":"10.3390/antibiotics13121173","DOIUrl":"https://doi.org/10.3390/antibiotics13121173","url":null,"abstract":"<p><p><b>Background:</b> The optimal antimicrobial treatment duration for diabetes-related foot osteomyelitis (DFO) currently needs to be determined. We systematically reviewed the effects of short and long treatment durations on outcomes of DFO. <b>Methods:</b> We performed a systematic review searching Cochrane, CENTRAL, MEDLINE, Embase, and CINAHL Plus from inception up to 19 January 2024. Two independent reviewers screened the titles and abstracts of the studies. Studies comparing short (<6 weeks) and long (>6 weeks) treatment durations for DFO were included. The primary outcome was amputation; the secondary outcomes were remission, mortality, costs, quality of life, and adverse events. Risk of bias and GRADE were assessed. <b>Results:</b> We identified 2708 references, of which 2173 remained after removing duplicates. Two studies were included. Differences in methodology precluded a meta-analysis. The primary outcome, major amputation, was reported in one study, with a rate of 10% in both the intervention and comparison groups (<i>p</i> = 1.00), regardless of treatment duration. For the secondary outcome, remission rates, the first study reported 60% in the intervention group versus 70% in the comparison group (<i>p</i> = 0.50). In the second study, remission rates were 84% in the intervention group versus 78% in the comparison group (<i>p</i> = 0.55). Data for the outcomes mortality, costs, and quality of life were not available. Short treatment duration may lead to fewer adverse events. The risk of bias was assessed as low to moderate, and the level of evidence ranged from very low to moderate. <b>Conclusions:</b> Our findings suggest that for DFO, there is no difference between a shorter and more prolonged duration of antimicrobial treatment regarding amputation and remission, with potentially fewer adverse events with shorter treatment durations. However, the uncertainty stems from limited, heterogeneous studies and generally low-quality evidence marred by moderate biases, imprecision, and indirectness. More high-quality studies are needed to substantiate these findings.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 12","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Antibiotics-BaselPub Date : 2024-12-04DOI: 10.3390/antibiotics13121171
José Weverton Almeida-Bezerra, Saulo Almeida Menezes, José Thyálisson da Costa Silva, Simone Galdino de Sousa, Daniel Sampaio Alves, Gabriel Gonçalves Alencar, Isaac Moura Araújo, Ewerton Yago de Sousa Rodrigues, Cícera Datiane de Morais Oliveira-Tintino, Rafael Pereira da Cruz, Janaína Esmeraldo Rocha, Saulo Relison Tintino, José Maria Barbosa-Filho, Maria Flaviana Bezerra Morais-Braga, Irwin Rose Alencar de Menezes, António Raposo, Henrique Douglas Melo Coutinho
{"title":"Analysis of the Antibiotic-Potentiating Activity, Absorption, Distribution, Metabolism, and Excretion (ADME) and the Molecular Docking Properties of Phytol Against Multi-Drug-Resistant (MDR) Strains.","authors":"José Weverton Almeida-Bezerra, Saulo Almeida Menezes, José Thyálisson da Costa Silva, Simone Galdino de Sousa, Daniel Sampaio Alves, Gabriel Gonçalves Alencar, Isaac Moura Araújo, Ewerton Yago de Sousa Rodrigues, Cícera Datiane de Morais Oliveira-Tintino, Rafael Pereira da Cruz, Janaína Esmeraldo Rocha, Saulo Relison Tintino, José Maria Barbosa-Filho, Maria Flaviana Bezerra Morais-Braga, Irwin Rose Alencar de Menezes, António Raposo, Henrique Douglas Melo Coutinho","doi":"10.3390/antibiotics13121171","DOIUrl":"https://doi.org/10.3390/antibiotics13121171","url":null,"abstract":"<p><p><b>Background:</b> Phytol is a diterpene from the long-chain unsaturated acyclic alcohols, known for its diverse biological effects, including antimicrobial and anti-inflammatory activities. Present in essential oils, phytol is a promising candidate for various applications in the pharmaceutical and biotechnological sectors. This study aimed to evaluate the <i>in vitro</i> antibacterial and drug-potentiating effects of phytol against multidrug-resistant bacteria and to evaluate its <i>in silico</i> properties: ADME and molecular docking. <b>Methods:</b> The <i>in vitro</i> antibacterial activity of phytol and the phytol combined with conventional drugs was evaluated by microdilution tests against standard and resistant bacterial strains. Finally, the SwissADME platform was employed to analyse the physicochemical and pharmacokinetic characteristics of phytol. <b>Results:</b> Phytol significantly reduced the Minimum Inhibitory Concentration (MIC) of norfloxacin and gentamicin required to inhibit multidrug-resistant strains of <i>Escherichia coli</i> and <i>Staphylococcus aureus</i>, respectively. Additionally, ADME analysis revealed that phytol exhibits low toxicity and favourable pharmacokinetic properties; in addition, it is revealed through molecular docking that phytol showed a relevant affinity with the proteins 6GJ1 and 5KDR, however, with values lower than the drugs gentamicin and ampicillin. <b>Conclusions:</b> Collectively, these findings suggest that phytol holds potential as an effective adjuvant in combating antimicrobial resistance.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 12","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Antibiotics-BaselPub Date : 2024-12-04DOI: 10.3390/antibiotics13121172
Amin A Aqel, Tala M Al-Matarneh, Tayf K Al-Tarawneh, Tahrir Alnawayseh, Mohammed Alsbou, Yasser Gaber
{"title":"Monitoring of Antibiotic Resistance Patterns Within Al-Karak Governmental Hospital, Jordan, in 2022.","authors":"Amin A Aqel, Tala M Al-Matarneh, Tayf K Al-Tarawneh, Tahrir Alnawayseh, Mohammed Alsbou, Yasser Gaber","doi":"10.3390/antibiotics13121172","DOIUrl":"https://doi.org/10.3390/antibiotics13121172","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Antimicrobial resistance is considered one of the foremost global public health challenges, and its prevalence is increasing. In Jordan, particularly in Al-Karak Governorate, there is a lack of sufficient data on antimicrobial resistance to make accurate assessments. The main aim of the current study was to evaluate antibiotic resistance trends in clinical specimens from 2022 and assess antibiotic resistance patterns. The emphasis on the WHO antibiotic classification as Access, Watch, and Reserved (AWaRe) was adopted in the current study. <b>Results</b>: Among Gram-positive bacteria, <i>Enterococcus faecalis</i> exhibited 100% susceptibility to nitrofurantoin and 96% to vancomycin, <i>Streptococcus viridans</i> exhibited 100% susceptibility to teicoplanin, while CoNS (coagulase-negative <i>Staphylococci</i>) showed moderate resistance to Trimethoprim + Sulfamethoxazole (63%) and clindamycin (47%). Among Gram-negative bacteria, <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> displayed high susceptibility to fosfomycin (<i>E. coli</i>: 95%, <i>K. pneumoniae</i>: 80%) and amikacin (<i>E. coli</i>: 93%, <i>K. pneumoniae</i>: 81%). Resistance was notable for trimethoprim + sulfamethoxazole (<i>E. coli</i>: 47%, <i>K. pneumoniae</i>: 53%) and nitrofurantoin (<i>K. pneumoniae</i>: 30%). <i>Pseudomonas aeruginosa</i> exhibited the highest proportion of XDR strains (15%), followed by <i>K. pneumoniae</i> (11%) and <i>E. coli</i> (4%), while PDR strains were found in <i>P. aeruginosa</i> (6%), <i>K. pneumoniae</i> (3%), and <i>E. coli</i> (0.6%). XDR was observed in 4% of CoNS and 3% of <i>S. viridans</i> (α), with <i>Staphylococcus aureus</i> exhibiting both XDR and PDR at 1%. <b>Methods</b>: A cross-sectional retrospective study of bacterial species and their antimicrobial susceptibility was carried out at a hospital in Al Karak, Jordan, from January to December of 2022, the study included 1187 isolates from all locations in Al-Karak Governmental Hospital. <b>Conclusions</b>: The significant prevalence of XDR and PDR strains in key pathogens, particularly <i>P. aeruginosa</i> and <i>K. pneumoniae</i>, underscores the need for a robust Antimicrobial Stewardship Program (ASP) and infection control measures at Al-Karak Governmental Hospital. High susceptibility in several Access group antibiotics (e.g., amikacin and nitrofurantoin) supports their prioritization in empirical therapy, while the emergence of resistance in Watch and Reserved antibiotics highlights the necessity for rational use. These findings are very important for adjusting the local strategies to lower the spread of resistant strains and improve clinical outcomes.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 12","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Antibiotics-BaselPub Date : 2024-12-04DOI: 10.3390/antibiotics13121178
Olja Šovljanski, Milica Aćimović, Teodora Cvanić, Vanja Travičić, Aleksandra Popović, Jelena Vulić, Gordana Ćetković, Aleksandra Ranitović, Ana Tomić
{"title":"An In Vitro Evaluation of Robin's Pincushion Extract as a Novel Bioactive-Based Antistaphylococcal Agent-Comparison to Rosehip and Black Rosehip.","authors":"Olja Šovljanski, Milica Aćimović, Teodora Cvanić, Vanja Travičić, Aleksandra Popović, Jelena Vulić, Gordana Ćetković, Aleksandra Ranitović, Ana Tomić","doi":"10.3390/antibiotics13121178","DOIUrl":"https://doi.org/10.3390/antibiotics13121178","url":null,"abstract":"<p><p><b>Introduction:</b> This study explores the bioactive properties of extracts obtained from Robin's pincushion (<i>Diplolepis rosae</i>) collected in Sokobanja, Serbia. <b>Results:</b> Comprehensive in vitro assessments reveal high concentrations of total phenolics (186.37 mg GAE/g), along with significant levels of carotenoids (44.10 μg β-car/g). Robin's pincushion exhibited superior antioxidant capacities across DPPH, ABTS, and reducing power assays, significantly outperforming comparable extracts from rosehip (<i>Rosa canina</i>) and black rosehip (<i>Rosa spinosissima</i>) in these activities. Additionally, high inhibitory effects were observed in antimicrobial assays, with the extract demonstrating minimal inhibitory concentrations (MIC) as low as 1.56 mg/mL against the <i>Staphylococcus</i> species. Notably, the extract achieved full bactericidal effect within 24 h in time-kill kinetic studies which additionally highlight its potent antistaphylococcal potential. <b>Materials and methods:</b> Analyzing their phytochemical profiles and evaluating their potential as antioxidant, anti-inflammatory, antihyperglycemic, and antimicrobial agents, wide-ranging evaluation of bioactivity of Robin's pincushion was conducted. <b>Conclusions:</b> These findings highlight Robin's pincushion as a promising natural source of bioactive compounds with potential applications in traditional and modern medicine for managing oxidative stress, inflammation, hyperglycemia, and microbial infections.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 12","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Antibiotics-BaselPub Date : 2024-12-03DOI: 10.3390/antibiotics13121170
Dragos Stefan Lazar, Maria Nica, Daniel Romeo Codreanu, Alma Gabriela Kosa, Lucian L Visinescu, Corneliu Petru Popescu, Ion Cristian Efrem, Simin Aysel Florescu, George Sebastian Gherlan
{"title":"A Possible Tool for Guiding Therapeutic Approaches to Urinary Infections with <i>Klebsiella pneumoniae</i>: Analyzing a Dataset from a Romanian Tertiary Hospital.","authors":"Dragos Stefan Lazar, Maria Nica, Daniel Romeo Codreanu, Alma Gabriela Kosa, Lucian L Visinescu, Corneliu Petru Popescu, Ion Cristian Efrem, Simin Aysel Florescu, George Sebastian Gherlan","doi":"10.3390/antibiotics13121170","DOIUrl":"https://doi.org/10.3390/antibiotics13121170","url":null,"abstract":"<p><p><b>Introduction:</b> The emergence of carbapenem-resistant pathogenic bacteria is a growing global public health concern. Carbapenem-resistant uropathogenic strains of <i>Klebsiella pneumoniae</i> can cause uncomplicated or complicated urinary tract infections, leading to a high risk of treatment failure and the spread of resistance determinants. The objectives of this 24-month study were to identify the prognostic characteristics of patients who were infected with carbapenem-resistant <i>Klebsiella pneumoniae</i> (<i>CRKpn</i>) and to create a tool to estimate the probability of a <i>CRKpn</i> infection before having the complete results of a patient's antibiogram. <b>Results:</b> We found that 41.6% of all urinary infections with <i>Kpn</i> were caused by <i>CRKpn</i>. Factors such as male gender, the presence of upper urinary tract infections, invasive urinary maneuvers, recent infection with or carriage of the germ, and the nosocomial occurrence of UTIs with <i>Kpn</i> were predictive for <i>CRKpn</i> infection. Based on these factors, we proposed a model to estimate the presence of <i>CRKpn</i>. <b>Methods:</b> A retrospective case-control study including all hospitalized patients with urinary tract infections (UTIs) caused by <i>Klebsiella pneumoniae</i> was carried out. We reported data as percentages, identified independent predictors of the presence of <i>CRKpn</i>, and proposed a tool to evaluate the probability through multivariate analysis. <b>Conclusions:</b> Through this study, we aim to provide clinicians with a tool to support decision making regarding first-line antibiotic treatment.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 12","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Antibiotics-BaselPub Date : 2024-12-03DOI: 10.3390/antibiotics13121166
Kaitlyn Weinert-Stein, Mackenzie Cater, Sree Sarah Cherian, Reem Azem, Ana E Khazan, Ankita P Desai, LeAnne Tripp, Peter Paul Lim, Lisa M Stempak, Leila S Hojat
{"title":"Clinical Utility of Broad-Range PCR Testing and Impact on Outcomes in Adults with Suspected Infection.","authors":"Kaitlyn Weinert-Stein, Mackenzie Cater, Sree Sarah Cherian, Reem Azem, Ana E Khazan, Ankita P Desai, LeAnne Tripp, Peter Paul Lim, Lisa M Stempak, Leila S Hojat","doi":"10.3390/antibiotics13121166","DOIUrl":"https://doi.org/10.3390/antibiotics13121166","url":null,"abstract":"<p><p><b>Background</b>: The development of broad-range polymerase chain reaction (BR-PCR) and next-generation sequencing techniques has significant implications for antimicrobial stewardship by increasing clinicians' ability to provide a tailored antimicrobial regimen. We sought to explore the clinical utility of BR-PCR testing and its impact on antimicrobial treatment among an adult cohort in a large hospital system. <b>Methods</b>: We retrospectively evaluated samples that underwent BR-PCR testing between 2017 and 2021 and summarized their clinical characteristics and impact on antimicrobial therapy. We identified BR-PCR testing as having clinical utility if the results led to adjustment of antimicrobial choice or duration or to confirmation of the initial empiric regimen, while no clinical utility was assigned to results that were negative or clinically insignificant, unavailable due to loss to follow-up, or lacking clinical indication (treatment completed before the test results returned or conventional cultures revealed the causative pathogen). <b>Results</b>: Among 359 specimens, BR-PCR was positive for 107 (30%). Clinical utility was identified for 106 (29.5%) specimens, including 45 with negative BR-PCR results. The rates of clinical utility varied based on the type of sample tested, with the highest clinical utility associated with cranial samples (60%), followed by body fluid (56%) and endovascular (54%) samples, and the lowest with CSF (15%) and bone and joint (19%) samples. We also identified many BR-PCR tests that were not clinically indicated (23.4%). <b>Conclusions</b>: This study highlights the utility of BR-PCR testing to support antimicrobial stewardship initiatives. Further studies are needed to identify clinical scenarios in which it is appropriate to order BR-PCR testing and for a careful interpretation of negative BR-PCR results.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 12","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Antibiotics-BaselPub Date : 2024-12-03DOI: 10.3390/antibiotics13121168
Aleksandra Bibow, Wiesław Oleszek
{"title":"Essential Oils as Potential Natural Antioxidants, Antimicrobial, and Antifungal Agents in Active Food Packaging.","authors":"Aleksandra Bibow, Wiesław Oleszek","doi":"10.3390/antibiotics13121168","DOIUrl":"https://doi.org/10.3390/antibiotics13121168","url":null,"abstract":"<p><p>In the last few years, there has been growing interest in the harmful impact of synthetic additives, the increased consumer focus on nutrition, and their unwillingness to use antibiotics and preservatives. The food industry has been driven to seek natural alternatives to synthetic antioxidants and integrate them into the production processes. Moreover, the most significant risk factor for foodborne illness is the consumption of raw or undercooked meats and milk, which may be contaminated with <i>Listeria</i> spp., <i>Campylobacter</i> spp., or <i>Salmonella</i> spp. This article presents a review of techniques for the functional properties of biopolymer particles loaded with essential oils that form a stable network to control their release, making them ideal for improving food packaging and processing. Such substances are employed in the manufacture of packaging materials and coated films and as emulsions, nanoemulsions, and coatings directly incorporated into the food matrix. It is of paramount importance to gain an understanding of the migration mechanism and potential interactions between packaging materials and foodstuffs. A more profound comprehension of the chemical constitution and biological characteristics of these extracts and their constituents would be advantageous for the identification of prospective applications in active food packaging. The findings of our study suggest the existence of certain constraints and deficiencies in the investigation of essential oils and their efficacy in food packaging. Consequently, further comprehensive research in this domain is imperative.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 12","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Antibiotics-BaselPub Date : 2024-12-03DOI: 10.3390/antibiotics13121169
Amaravadhi Harikishore, Gerhard Grüber
{"title":"<i>Mycobacterium tuberculosis</i> F-ATP Synthase Inhibitors and Targets.","authors":"Amaravadhi Harikishore, Gerhard Grüber","doi":"10.3390/antibiotics13121169","DOIUrl":"https://doi.org/10.3390/antibiotics13121169","url":null,"abstract":"<p><p><i>Mycobacteria tuberculosis</i> (<i>Mtb</i>) infection causes tuberculosis (TB). TB is one of the most intractable infectious diseases, causing over 1.13 million deaths annually. Under harsh growing conditions, the innate response of mycobacteria is to shut down its respiratory metabolism to a basal level, transit into a dormant, non-replicating phase to preserve viability, and establish latent infection. <i>Mtb</i> utilizes non-canonical regulatory mechanisms, such as alternative oxidase pathways, to survive in low oxygen/nutrient conditions. The bacterium's survival in its native microenvironmental niches is aided by its ability to evolve mutations to drug binding sites, enhance overexpression of various enzymes that activate β-lactam antibiotics hydrolysis, or stimulate efflux pathways to ward off the effect of antibiotics. Bedaquiline and its 3,5-dialkoxypyridine analogs, sudapyridine and squaramide S31f, have been shown to be potent <i>Mtb</i> F<sub>1</sub>F<sub>O</sub>-ATP synthase inhibitors of replicating and non-replicating <i>Mtb</i> and have brought oxidative phosphorylation into focus as an anti-TB target. In this review, we attempt to highlight non-canonical structural and regulatory pathogen-specific epitopes of the F<sub>1</sub>-domain, ligand development on such sites, structural classes of inhibitors targeting the Fo-domain, and alternative respiratory metabolic responses that <i>Mtb</i> employs in response to bedaquiline to ensure its survival and establish latent infection.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 12","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Antibiotics-BaselPub Date : 2024-12-03DOI: 10.3390/antibiotics13121167
Vera A Alferova, Anna A Baranova, Olga A Belozerova, Evgeny L Gulyak, Andrey A Mikhaylov, Yaroslav V Solovev, Mikhail Y Zhitlov, Arseniy A Sinichich, Anton P Tyurin, Ekaterina A Trusova, Alexey V Beletsky, Andrey V Mardanov, Nikolai V Ravin, Olda A Lapchinskaya, Vladimir A Korshun, Alexander G Gabibov, Stanislav S Terekhov
{"title":"Molecular Decoration and Unconventional Double Bond Migration in Irumamycin Biosynthesis.","authors":"Vera A Alferova, Anna A Baranova, Olga A Belozerova, Evgeny L Gulyak, Andrey A Mikhaylov, Yaroslav V Solovev, Mikhail Y Zhitlov, Arseniy A Sinichich, Anton P Tyurin, Ekaterina A Trusova, Alexey V Beletsky, Andrey V Mardanov, Nikolai V Ravin, Olda A Lapchinskaya, Vladimir A Korshun, Alexander G Gabibov, Stanislav S Terekhov","doi":"10.3390/antibiotics13121167","DOIUrl":"https://doi.org/10.3390/antibiotics13121167","url":null,"abstract":"<p><p>Irumamycin (Iru) is a complex polyketide with pronounced antifungal activity produced by a type I polyketide (PKS) synthase. Iru features a unique hemiketal ring and an epoxide group, making its biosynthesis and the structural diversity of related compounds particularly intriguing. In this study, we performed a detailed analysis of the <i>iru</i> biosynthetic gene cluster (BGC) to uncover the mechanisms underlying Iru formation. We examined the <i>iru</i> PKS, including the domain architecture of individual modules and the overall spatial structure of the PKS, and uncovered discrepancies in substrate specificity and iterative chain elongation. Two potential pathways for the formation of the hemiketal ring, involving either an olefin shift or electrocyclization, were proposed and assessed using <sup>18</sup>O-labeling experiments and reaction activation energy calculations. Based on our findings, the hemiketal ring is likely formed by PKS-assisted double bond migration and TE domain-mediated cyclization. Furthermore, putative tailoring enzymes mediating epoxide formation specific to Iru were identified. The revealed Iru biosynthetic machinery provides insight into the complex enzymatic processes involved in Iru production, including macrocycle sculpting and decoration. These mechanistic details open new avenues for a targeted architecture of novel macrolide analogs through synthetic biology and biosynthetic engineering.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 12","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Antibiotics-BaselPub Date : 2024-12-03DOI: 10.3390/antibiotics13121164
Veronica Montesinos-Cruz, Greg A Somerville
{"title":"Shining a Light on Spectrophotometry in Bacteriology.","authors":"Veronica Montesinos-Cruz, Greg A Somerville","doi":"10.3390/antibiotics13121164","DOIUrl":"https://doi.org/10.3390/antibiotics13121164","url":null,"abstract":"<p><p>Spectrophotometry is widely used in biological sciences. In bacteriology, spectrophotometric monitoring of cell numbers during cultivation provides a rapid assessment of growth. Unfortunately, familiarity with this technique has led scientists to become complacent in its usage. Here, we review some guiding principles of spectrophotometry and practical considerations that may influence the outcome of experiments. This perspective is intended to assist both new and seasoned scientists in presenting robust and reproducible growth data based on spectrophotometric readings.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 12","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}