Microbiology spectrum最新文献

{"title":"The combinations of cefazolin with linezolid and cefazolin with clindamycin are indifferent against methicillin-susceptible <i>Staphylococcus aureus</i>.","authors":"Madeline Mellett, Julia Van Riel, Rachel Corsini, Sarah Satola, Alexander Lawandi, Chelsea Caya, Sebastiaan J van Hal, Todd C Lee, Jesse Papenburg, Cedric P Yansouni, Ahmed Babiker, Matthew P Cheng","doi":"10.1128/spectrum.01763-25","DOIUrl":"https://doi.org/10.1128/spectrum.01763-25","url":null,"abstract":"<p><p>Antimicrobial combinations resulting in synergy against <i>Staphylococcus aureus</i> are desirable for improving clinical efficacy in the treatment of severe infections caused by this pathogen. Despite an existing biological rationale for the combination of cefazolin and linezolid for methicillin-susceptible <i>S. aureus</i> (MSSA), this combination has yet to be evaluated for <i>in vitro</i> synergy. We employed the checkerboard and E-test methods of synergy assessment to evaluate cefazolin in combination with linezolid against 19 clinical MSSA isolates from two centers and compared the findings to cefazolin in combination with another protein synthesis inhibitor, clindamycin. Synergy was determined using the fractional inhibitory concentration index (FICI) through both the checkerboard and combined E-test assays. Combinations of cefazolin with linezolid and clindamycin demonstrated indifference through both methods (median checkerboard FICI of 1.11 and 1.25 and median E-test FICI of 0.99 and 0.88, respectively). Although the studied combinations were not synergistic, results of both assays were categorically consistent and suggest that the E-test is a robust method for evaluating synergy in <i>S. aureus</i> isolates.IMPORTANCEThe combinations of cefazolin and linezolid and cefazolin with clindamycin are potentially clinically relevant combinations for the treatment of severe <i>S. aureus</i> infections. However, the synergistic effects of these combinations against clinical MSSA isolates have not been previously determined. We performed checkerboard and E-test synergy testing and demonstrated that these combinations were indifferent for MSSA isolates. Although synergy was not identified for these combinations, the methods of synergy assessment agreed, highlighting the potential benefit for the combined gradient diffusion assay in future synergy assessment. Due to ease of use and categorical agreement with the checkerboard method in this study, this method may be beneficial for further implementation in synergy testing, leading to the identification of synergistic combinations that may improve treatment success for severe <i>S. aureus</i> infections.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0176325"},"PeriodicalIF":3.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Restoring colistin sensitivity in colistin-resistant gram-negative bacteria: combinatorial use of α-terpineol and colistin.","authors":"Yuhan Yang, Panjie Hu, Yanchun Gong, Zeyong Zhong, Yichi Zhang, Fan Ye, Tieli Zhou, Jianming Cao, Zhongyong Wang","doi":"10.1128/spectrum.00825-25","DOIUrl":"https://doi.org/10.1128/spectrum.00825-25","url":null,"abstract":"<p><p>Multidrug-resistant gram-negative bacteria (GNB) have posed a serious public health hazard worldwide. Colistin (COL), the ultimate therapeutic option for treating GNB infections, has had escalating resistance rates concomitant with increased utilization. In this study, we attempted to increase the sensitivity to COL using a plant extract, α-terpineol (α-TP). Checkerboard and time-kill assays indicated that the combination of COL and α-TP exhibited pronounced synergistic antimicrobial effects against colistin-resistant (COL-R) GNB <i>in vitro</i>. Biofilm assessments revealed that COL combined with α-TP effectively inhibited biofilm development and eliminated established biofilms. Scanning electron microscopy indicated substantial disruption of bacterial cell membranes after 6 h of combined treatment. Additionally, cytotoxicity and erythrocyte hemolysis assays confirmed that α-TP maintained a degree of safety at synergistic concentrations. Mechanistically, the combination of COL and α-TP promoted the accumulation of reactive oxygen species and enhanced the permeability of both the inner and outer bacterial membranes. This study demonstrated that α-TP can restore the sensitivity of COL-R GNB to COL when used in combination.</p><p><strong>Importance: </strong>Colistin (COL) has emerged as a last-line therapeutic agent for gram-negative bacteria (GNB) infections. However, widespread antibiotic use has led to an alarming increase in the number of colistin-resistant (COL-R) strains. In this study, we demonstrate that combining COL with a plant-derived extract could effectively restore the susceptibility of COL-R GNB. A possible treatment plan for COL-R GNB is presented.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0082525"},"PeriodicalIF":3.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergence of ST8-USA300 and ST8-USA300-Latin American variant: a changing landscape of community-associated methicillin-resistant <i>Staphylococcus aureus</i> in Chile.","authors":"Alejandro Aguayo-Reyes, Felipe Morales-León, Mario Quezada-Aguiluz, Andrés Opazo-Capurro, Helia Bello-Toledo, Sergio Mella, Néstor Herrera-Chávez, Maximiliano Matus-Köhler, Juan Carlos Hormazábal, Gerardo González-Rocha","doi":"10.1128/spectrum.01031-25","DOIUrl":"https://doi.org/10.1128/spectrum.01031-25","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i> is a versatile pathogen capable of causing various infections. Since the 1960s, the emergence of methicillin-resistant <i>S. aureus</i> (MRSA) has posed a significant challenge due to its antibiotic resistance. Among these, community-associated MRSA (CA-MRSA) emerged in the 1990s, which traditionally harbors the <i>mecA</i> gene and the Panton-Valentine leukocidin, affecting individuals without traditional risk factors. In this study, we aimed to describe the genetic and phenotypic characteristics of 54 CA-MRSA isolates circulating in Chile, collected between 2007 and 2023 from various healthcare centers across the country. All strains carried <i>mecA</i>, with SCC<i>mec</i> IVc being the most prevalent (67%). The predominant clone was USA300-Latin American variant (USA300-LV) (ST8-SCC<i>mec</i> IVc-COMER+) 43%, followed by USA300 (ST8-SCC<i>mec</i> IVa-ACME+) 15%, ST30-SCC<i>mec</i> IVc (15%), and ST5-SCC<i>mec</i> IVa (9%). All isolates were resistant to cefoxitin, and some exhibited additional resistance to erythromycin (18%), clindamycin (2%), and tetracycline (2%). Further studies on the molecular epidemiology of CA-MRSA in Chile should be performed, as our results evidenced the clonal nature and evolution of CA-MRSA in Chile, where the circulation of the ST8-USA300 and ST8-USA300-LV lineages in the community represents a serious threat for national public health.</p><p><strong>Importance: </strong>The emergence of community-associated methicillin-resistant <i>Staphylococcus aureus</i> (CA-MRSA) poses a significant public health threat. Unlike hospital-associated strains, CA-MRSA affects healthy individuals outside healthcare settings, often resulting in severe infections. The World Health Organization has designated MRSA as a priority pathogen due to its association with life-threatening infections worldwide. The increasing prevalence of CA-MRSA strains, particularly those resistant to multiple antibiotics, further complicates treatment efforts. Our findings highlight the predominance of the ST8-USA300 and ST8-USA300-Latin American variant clones in Chile, indicating the ongoing evolution of CA-MRSA in the region and suggesting the potential establishment of these clones within the community. Monitoring the spread and genetic diversity of these strains is essential for developing targeted interventions and informing public health strategies to control this pathogen and mitigate its impact on national health.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0103125"},"PeriodicalIF":3.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance analysis of the GeneXpert respiratory panel prototype assay for the diagnosis of viral and bacterial upper respiratory tract infections.","authors":"Linda M W Chan, Michael Tang, Eddie C M Leung, Nicole Y Y Lee, Viola C Y Chow","doi":"10.1128/spectrum.02560-24","DOIUrl":"https://doi.org/10.1128/spectrum.02560-24","url":null,"abstract":"<p><p>GeneXpert respiratory panel (GX-RP) is a new <i>in vitro</i> qualitative multiplexed nucleic acid amplification test designed to simultaneously detect and identify 26 common respiratory pathogens from nasopharyngeal swabs (NPSs) in patients exhibiting signs and symptoms of upper respiratory tract infection. This is a retrospective study that compares the prototype assay with two FDA-approved respiratory panels-the BioFire FilmArray (FA) Respiratory 2.1 plus and Hologic Panther Fusion (PF) respiratory assay. A total of 292 NPS specimens from patients with upper respiratory tract infection symptoms were collected from three hospitals in Hong Kong, SAR. There was concordance in 269/292 specimens (92.1%), reaching full agreement with Influenza A, <i>Bordetella pertussis,</i> and <i>Mycoplasma pneumoniae</i>. Among the discordant specimens, 7 specimens were only positive for GX-RP, and 16 specimens were only positive for their comparators. Codetections were present in 60.9% of the discordant results. GX-RP has an overall positive percent agreement of 93.1%, negative percent agreement of 99.9%, and a prevalence-adjusted bias-adjusted kappa of 99.0%. It showed good agreement when compared with FA respiratory panel or PF respiratory assay.IMPORTANCEMultiplex respiratory pathogen panels are a diagnostic mainstay in patients with upper respiratory tract symptoms. New platforms and improved versions of previous platforms emerge over time. Early evaluation of their diagnostic performance using real-world data is essential for the necessary revisions to be made, which would facilitate public access to improved panels. Our retrospective study provides preliminary evidence that the GeneXpert respiratory panel prototype assay has comparable performance to the BioFire FilmArray and Hologic Panther Fusion respiratory assays and may be an additional candidate in our future toolkit against upper respiratory tract pathogens.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0256024"},"PeriodicalIF":3.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics and treatment outcomes of <i>Acinetobacter baumannii</i> bloodstream infections in a setting with high carbapenem susceptibility among isolates.","authors":"Jinghao Nicholas Ngiam, Matthew Chung Yi Koh, Ka Lip Chew","doi":"10.1128/spectrum.01607-25","DOIUrl":"https://doi.org/10.1128/spectrum.01607-25","url":null,"abstract":"<p><p>In most settings, carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB) infections predominate over carbapenem-susceptible <i>Acinetobacter baumannii</i> (CSAB). Treatment guidelines focus on the management of CRAB and do not describe the optimal antibiotic choice for CSAB. We describe the clinical characteristics and outcomes in both CRAB and CSAB. We examined consecutive episodes of CRAB or CSAB bloodstream infections in our institution from February 2022 to July 2024. Clinical, laboratory, and microbiological data were tabulated, and adverse outcomes were defined as the need for intensive care (ICU) or all-cause in-hospital mortality. We compared (i) CRAB to CSAB, and among patients with CSAB, (ii) we evaluated if the definitive antibiotic choice was associated with adverse outcomes, after adjusting for C-reactive protein levels. We identified 71 unique episodes of bacteremia, of which a majority (52/71, 73.2%) were nosocomial onset. A minority were CRAB (15/71, 21.1%). These patients often had ICU onset, prior carbapenem exposure, and were more likely to experience mortality (73.3% versus 16.1%, <i>P</i> < 0.001). Only a minority of patients (7/71, 9.9%) received dual antibiotic therapy. Among the 56 patients with CSAB, only 11/56 (19.6%) experienced adverse outcomes. On multivariable analysis, after adjusting for elevated C-reactive protein, the use of carbapenems as the definitive antibiotic choice remained independently associated with adverse outcomes (adjusted odds ratio 7.34, 95% CI 1.25-43.01, <i>P</i> = 0.027). CSAB was far more common than CRAB in our setting. Prior carbapenem exposure and ICU onset were important risk factors for CRAB, which had higher mortality than CSAB. Carbapenem-sparing options may be considered as the definitive antibiotic choice for CSAB.</p><p><strong>Importance: </strong>In our setting, carbapenem-susceptible <i>Acinetobacter baumannii</i> (CSAB, <i>n</i> = 56/71, 78.9%) bloodstream infections (BSIs) were far more common than with carbapenem-resistant isolates (CRAB). CRAB BSI was associated with intensive care onset, prior carbapenem use, and had higher mortality (73.3% versus 16.1%). In CSAB BSI, after adjusting for elevated C-reactive protein, the definitive use of carbapenems for treatment remained independently associated with adverse outcomes (adjusted odds ratio 7.34, 95%CI 1.25-43.01). These findings may suggest that carbapenem-sparing regimens may be effective alternative antibiotic choices for CSAB. Although treatment guidelines focus on CRAB, future prospective studies should also evaluate optimal treatment strategies for CSAB.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0160725"},"PeriodicalIF":3.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of leptospiral virulence-modifying protein detection assay: implications for pathogenesis and diagnostic test development.","authors":"Reetika Chaurasia, Andrea Jacobs, Jie Tang, Songyu Dong, Joseph M Vinetz","doi":"10.1128/spectrum.00018-25","DOIUrl":"https://doi.org/10.1128/spectrum.00018-25","url":null,"abstract":"<p><p>Leptospirosis, a globally significant neglected tropical disease, continues to lack early and reliable diagnostic methods despite over a century since the discovery of the disease and its etiological agent. Previously, we identified the pathogen-specific paralogous PF07598 gene family encoding virulence-modifying (VM) exotoxins, which play a critical role in leptospirosis pathogenesis. In this study, we developed a monoclonal antibody (mAb)-based capture immunoassay that detects VM proteins in the blood of experimental hamster models, validating the hypothesis that VM proteins function as secretory exotoxins that mediate disease pathogenesis. Monoclonal antibodies were generated against a natural variant, LA0591, a VM protein containing a conserved C-terminal DNase toxin domain but lacking N-terminal ricin B-like lectin domains. Epitope mapping identified specific linear epitopes targeted by mAbs 5F8, 5G10, and 6A5, with distinct binding regions confirmed through binning and peptide mapping. These mAbs demonstrated high-affinity binding to homologous antigens, with sub-picomolar dissociation constants (K_d = 1.41E-09 for 5F8 and K_d <1.0E-12 for 5G10 and 6A5) and cross-reacted with full-length recombinant VM proteins expressed in <i>E. coli</i>. Immunoblotting revealed increased expression of VM proteins by <i>L. interrogans</i> serovar Copenhageni strain L1-130 under <i>in vivo</i>-like conditions. Using mAbs 6A5 and 5F8, a capture ELISA detected circulating VM proteins in the serum and urine from infected hamsters, confirming the secretion of these proteins during infection. This study provides the first evidence of secreted leptospiral exotoxins in the bloodstream of infected animals, advancing the understanding of leptospirosis pathogenesis and establishing a basis for developing novel diagnostic approaches.</p><p><strong>Importance: </strong>This research addresses the global health issue of leptospirosis, a neglected tropical disease that still lacks early and reliable diagnostic methods despite being known for over a century. The study has developed a novel test using specially designed antibodies to detect specific proteins related to the disease in the blood of infected hamsters. These proteins are linked to the pathogen's ability to cause illness. The successful detection of these proteins in the bloodstream is a significant advancement, as it not only improves our understanding of the disease's progression but also lays the groundwork for developing new diagnostic tools. This could lead to earlier and more accurate diagnoses of leptospirosis, potentially saving lives and reducing the impact of the disease globally.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0001825"},"PeriodicalIF":3.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curli-independent defense against <i>Bdellovibrio bacteriovorus</i> in <i>E. coli</i>.","authors":"Ryan Sayegh, Hannah E Ledvina, Aaron T Whiteley","doi":"10.1128/spectrum.00342-25","DOIUrl":"https://doi.org/10.1128/spectrum.00342-25","url":null,"abstract":"<p><p>Predatory bacteria are a group of organisms that use diverse methods to access nutrients and grow by killing prey bacteria. The predator <i>Bdellovibrio bacteriovorus</i> is capable of preying on a wide range of gram-negative bacteria by invading the periplasmic space, killing, digesting, and ultimately lysing prey cells. <i>B. bacteriovorus</i>, like a phage, replicates at the expense of its host, yet unlike phage defense, there are few characterized mechanisms for bacteria to resist <i>B. bacteriovorus</i>. Previously, we discovered that an extracellular amyloid protein called curli protects <i>Escherichia coli</i> from <i>B. bacteriovorus</i>. Here, we searched for additional modes of <i>B. bacteriovorus</i> resistance and identified a strain within the <i>E. coli</i> Reference (ECOR) collection, ECOR29, that uses a curli-independent mechanism that requires lipopolysaccharide (LPS)-modifying enzymes for defense. Over 30% of the ECOR collection is resistant to <i>B. bacteriovorus</i>. We successfully deleted the gene encoding the major curli subunit in many of these, and only ECOR29 remained resistant. We hypothesized that ECOR29 encoded an alternative resistance mechanism and identified determinants of defense using a forward genetic screen. Our screen revealed critical roles for enzymes that modify LPS, alter the outer membrane, and are homologous to plasmid partitioning systems. Examination of ECOR29 by electron microscopy did not identify overt phenotypes or visible alterations to extracellular structures. We also were unable to identify any secreted factors that impacted <i>B. bacteriovorus</i> viability. Our work demonstrates that <i>E. coli</i> encode curli-independent mechanisms that restrict <i>B. bacteriovorus</i> and expand our understanding of the antipredatory bacteria arm of the bacterial immune system.IMPORTANCEUnderstanding host-pathogen interactions has the potential to illuminate fundamental aspects of biology. Here, we investigate an atypical host-pathogen system, the interaction between <i>Escherichia coli</i> and the predatory bacterium <i>Bdellovibrio bacteriovorus. B. bacteriovorus</i> has a unique predatory life cycle that requires intimate interactions with the outer membrane, periplasm, peptidoglycan, and inner membrane of prey cells. Accordingly, understanding mechanisms of <i>B. bacteriovorus</i> predation and resistance will help us to better understand the gram-negative cell envelope, an ideal target for novel antibacterial compounds. Predatory bacteria are abundant and ubiquitous threats to bacteria in a wide variety of environments. Further findings from experiments in this field will expand our understanding of some of the most basic aspects of the microbial world.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0034225"},"PeriodicalIF":3.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EccC3 is essential for pathogenesis of rough <i>Mycobacterium abscessus</i> in zebrafish.","authors":"Yara Tasrini, Wassim Daher, Laurent Kremer","doi":"10.1128/spectrum.01949-25","DOIUrl":"https://doi.org/10.1128/spectrum.01949-25","url":null,"abstract":"<p><p><i>Mycobacterium abscessus</i> (<i>Mab</i>) is an emerging human pathogen causing severe lung infections in cystic fibrosis patients and displays either a smooth (S) or a rough (R) morphotype, the latter being associated with a strong inflammatory response. In contrast to most other mycobacteria, it possesses only two ESX secretion systems, ESX-3 and ESX-4. Recent work showed that infection of <i>Mab</i> S lacking the <i>eccC3</i>-encoding ATPase component of ESX-3 in mice was associated with reduced bacterial loads in lungs and no mortality. While these studies emphasize the importance of ESX-3 in the virulence of <i>Mab</i> S, its contribution to the pathogenesis of <i>Mab</i> R <i>in vivo</i> remains undefined. Here, we exploited an <i>Mab</i> R mutant lacking <i>eccC3</i> using the zebrafish model, particularly suited to describe the chronology and pathophysiological signs of <i>Mab</i> R infection. Our results clearly show that R Δ<i>eccC3</i> was highly attenuated in larvae, as evidenced by the enhanced larvae survival, the reduced bacterial burden, cord number, and limited proportion of abscesses, while functional complementation of <i>eccC3</i> partially restored the phenotypes to wild-type levels. The phenotypes were corroborated with whole larvae imaging, showing lower bacterial foci in R Δ<i>eccC3</i>, as compared to the parental R strain. Moreover, infection with R Δ<i>eccC3</i> was associated with a lower pro-inflammatory response, as showcased by the reduced production of <i>il1b</i> and <i>tnfa</i> transcripts. Together, these findings demonstrate that ESX-3 is a primary driver of <i>Mab</i> R pathogenicity.IMPORTANCE<i>Mycobacterium abscessus</i> (<i>Mab</i>) is currently recognized as an extremely difficult-to-manage pathogen in patients with cystic fibrosis. The rough (R) morphotype of <i>Mab</i> is associated with chronic and more aggressive infections in patients than the smooth (S) morphotype. However, the mechanisms of pathogenesis of <i>Mab</i> R remain largely unexplored. In this study, we investigated the infection capacity and virulence of a <i>Mab</i> R mutant lacking a functional ESX-3 secretion system using the zebrafish model. The mutant was severely impaired in its ability to replicate in the larvae, and this was correlated with a significant increase in larvae survival, highlighting the critical role of ESX-3 in <i>Mab</i> R virulence. Overall, this emphasizes ESX-3 as an attractive drug target for future drug developments against <i>Mab</i> R lung diseases.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0194925"},"PeriodicalIF":3.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"D-histidine exhibited anti-biofilm activity against <i>Aggregatibacter actinomycetemcomitans</i>.","authors":"Wenwen Shan, Fen Du, Haichuan Zhang, Jing Zhang, Xinyi Hu, Xinjiong Fan, Wuli Li","doi":"10.1128/spectrum.01216-25","DOIUrl":"https://doi.org/10.1128/spectrum.01216-25","url":null,"abstract":"<p><p><i>Aggregatibacter actinomycetemcomitans</i> is a key pathogen implicated in periodontitis. The bacterium in biofilms exhibits significant resistance to antimicrobial agents and host immune responses compared to its planktonic form, posing a major challenge for periodontal therapy. Recently, D-histidine has emerged as a promising anti-biofilm agent against <i>Pseudomonas aeruginosa</i> infections. However, its potential application in the oral field remains unexplored. This study investigated the anti-biofilm effect of D-histidine on <i>A. actinomycetemcomitans</i> and examined its influence on the expression of virulence factor genes to elucidate possible underlying mechanisms. Our results demonstrated that D-histidine inhibited biofilm formation and disrupted established biofilms in a concentration-dependent manner, without affecting bacterial growth. Furthermore, D-histidine downregulated the expression of virulence factors by inhibiting quorum sensing (QS)-related genes. Notably, combining D-histidine with antibiotics, such as amoxicillin, minocycline, and metronidazole, synergistically enhanced biofilm eradication and enabled the use of lower antibiotic dosages. These findings support the further evaluation of D-histidine as a potential anti-biofilm agent in the treatment of periodontitis.IMPORTANCEThe increasing prevalence of antibiotic-resistant <i>A. actinomycetemcomitans</i> biofilms posed a significant challenge in periodontitis management. This study demonstrated that D-histidine effectively targeted <i>A. actinomycetemcomitans</i> biofilms by disrupting structural integrity and suppressing virulence gene expression, without exerting bactericidal effects that could promote resistance development. Notably, D-histidine showed potent synergy with minocycline, significantly enhancing biofilm eradication while potentially enabling reduced antibiotic dosages. These findings established D-histidine as a promising adjunctive therapeutic agent, addressing the urgent need for novel approaches to overcome biofilm-associated antibiotic tolerance in periodontal treatment.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0121625"},"PeriodicalIF":3.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral β-lactam combinations are effective <i>in vitro</i> against <i>Mycobacterium avium</i>, regardless of clarithromycin susceptibility.","authors":"Maiko Yoshikawa, Tomoyasu Nishimura, Kana Misawa, Rina Shimamura, Kenta Suzuki, Shoko Kashimura, Yuki Igarashi, Yuki Enoki, Kazuaki Taguchi, Naoki Hasegawa, Ho Namkoong, Kazuaki Matsumoto","doi":"10.1128/spectrum.02012-25","DOIUrl":"https://doi.org/10.1128/spectrum.02012-25","url":null,"abstract":"<p><p>The global incidence and prevalence of pulmonary disease caused by the <i>Mycobacterium avium</i> complex (MAC), mainly comprising <i>M. avium</i> and <i>Mycobacterium intracellulare</i>, is increasing. However, treating MAC pulmonary disease is challenging in cases of clarithromycin (CLR)-resistant MAC or where the patients experience adverse effects or drug interactions with the few available antibiotics. Therefore, developing novel and highly effective antibiotics against MAC is crucial. Although the efficacy of dual β-lactams against <i>Mycobacterium abscessus</i> has been receiving attention, the efficacy of dual β-lactams against MAC remains unclear. Here, we used MAC type strains and clinical isolates to determine whether dual β-lactams were effective against MAC and which combinations synergistically inhibited bacterial growth using a broth microdilution checkerboard assay with 6 oral and 22 intravenous antibiotics. The combination effect and antibacterial activity differed between <i>M. avium</i> and <i>M. intracellulare</i>. Five combinations of oral β-lactams and 78 combinations of intravenous β-lactams showed a synergistic effect against the <i>M. avium</i> type strain. Among the <i>M. avium</i> clinical isolates, faropenem combined with cefuroxime showed the highest synergistic effect, and amoxicillin combined with tebipenem showed the lowest minimum inhibitory concentration. There was no significant difference in the combination effects between the CLR-susceptible and CLR-resistant <i>M. avium</i> clinical isolates in these pairs. In conclusion, regardless of CLR susceptibility, the oral β-lactam combinations were effective against <i>M. avium</i>. Thus, when treating MAC pulmonary disease, it is crucial to determine whether <i>M. avium</i> or <i>M. intracellulare</i> is the cause.IMPORTANCE<i>Mycobacterium avium</i> complex causes chronic respiratory infections, but treatment is often limited by drug resistance, intolerance, or interactions. As new therapeutic strategies are urgently needed, we focused on β-lactam antibiotics, which are widely used and well tolerated. Although dual β-lactams are effective against <i>Mycobacterium abscessus</i>, their utility against <i>Mycobacterium avium</i> complex has remained largely unexplored. Our <i>in vitro</i> study revealed that several β-lactam combinations are effective against <i>Mycobacterium avium</i>, regardless of drug resistance, indicating potential for clinical use. In contrast, <i>Mycobacterium intracellulare</i> showed lower susceptibility to β-lactams. Given this difference in drug susceptibility, we emphasize the clinical need to distinguish <i>Mycobacterium avium</i> and <i>Mycobacterium intracellulare</i> to optimize treatment of <i>Mycobacterium avium</i> complex pulmonary disease.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0201225"},"PeriodicalIF":3.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}