Microbiology spectrum最新文献

{"title":"The tradeoffs between persistence and mutation rates at sub-inhibitory antibiotic concentrations in <i>Staphylococcus aureus</i>.","authors":"Alysha S Ismail, Brandon A Berryhill, Teresa Gil-Gil, Joshua A Manuel, Andrew P Smith, Fernando Baquero, Bruce R Levin","doi":"10.1128/spectrum.02479-24","DOIUrl":"10.1128/spectrum.02479-24","url":null,"abstract":"<p><p>The rational design of the antibiotic treatment of bacterial infections employs these drugs to reach concentrations that exceed the minimum needed to prevent the replication of the target bacteria. However, within a treated patient, spatial and physiological heterogeneity promotes antibiotic gradients such that the concentration of antibiotics at specific sites is below the minimum needed to inhibit bacterial growth. Here, we investigate the effects of sub-inhibitory antibiotic concentrations on three parameters central to bacterial infection and the success of antibiotic treatment, using <i>in vitro</i> experiments with <i>Staphylococcus aureus</i> and mathematical and computer-simulation models. Our results, using drugs of six different classes, demonstrate that exposure to sub-inhibitory antibiotic concentrations alters bacterial growth dynamics, increases the mutation rate to antibiotic resistance, and decreases the production of persister cells thereby reducing persistence levels. Understanding this trade-off between mutation rates and persistence levels resulting from sub-inhibitory antibiotic exposure is crucial for optimizing, and mitigating the failure of, antibiotic therapy.</p><p><strong>Importance: </strong>Much of the research on antibiotics and antibiotic treatment has focused on drug concentrations sufficient to prevent the growth of bacteria. These concentrations, however, are not always reached everywhere in the body. Here, we look at the effects of exposure to these low concentrations of antibiotics on the common clinically important pathogen <i>Staphylococcus aureus</i>. We confirm a previous finding that sub-inhibitory antibiotic exposure decreases the total growth and the growth rate of the bacteria. Moreover, we demonstrate that the level of persistence, an important mechanism for bacteria to survive antibiotics, is decreased due to sub-inhibitory exposure. However, we find that the rate of generation of resistant mutants is substantially increased. Taken together, these results reveal an important trade-off that emerges as a consequence of bacteria being exposed to sub-inhibitory concentrations of antibiotics.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0247924"},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542543","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":"Association between nirmatrelvir/ritonavir treatment and antibiotic prescribing in the outpatient setting among patients with COVID-19.","authors":"Aisling R Caffrey, Haley J Appaneal, Vrishali V Lopes, Thomas Lavoie, Laura Puzniak, Evan J Zasowski, Luis Jodar, Iqra Arham, Kerry L LaPlante, John M McLaughlin","doi":"10.1128/spectrum.03209-24","DOIUrl":"10.1128/spectrum.03209-24","url":null,"abstract":"<p><p>Coronavirus disease 2019 (COVID-19) has complicated the management of acute respiratory infections and impacted antibiotic use. We assessed the relationship between nirmatrelvir/ritonavir (NMV/r) receipt and outpatient antibiotic prescribing among patients with COVID-19 in a large national health system. We conducted a retrospective cohort study among outpatients enrolled in the Veterans Affairs Healthcare System who had a positive severe acute respiratory syndrome coronavirus 2 test or COVID-19 diagnosis and were eligible for NMV/r treatment between 1 April 2022 and 31 March 2024. NMV/r-treated patients were compared with those who did not receive NMV/r and were considered unexposed until NMV/r was dispensed. We assessed the relationship between NMV/r receipt and being prescribed an outpatient antibiotic in the 30 days after a COVID-19 diagnosis using adjusted Cox proportional hazards regression. We included 302,600 NMV/r-eligible outpatients with COVID-19, of whom 67,649 received NMV/r and 234,951 did not receive NMV/r. NMV/r-treated patients were less likely to receive outpatient antibiotics compared to those who did not receive NMV/r (7.2% [4,901/67,649] vs 9.2% [21,533/234,951], respectively; adjusted hazard ratio [HR] 0.65, 95% CI: 0.63‒0.68). After excluding patients who received an antibiotic prescription upon COVID-19 diagnosis (i.e., likely empiric therapy), this relationship was attenuated (HR: 0.91, 95% CI: 0.87‒0.95). NMV/r-eligible patients with COVID-19 who received NMV/r were 35% less likely to be prescribed outpatient antibiotics compared to patients who did not receive NMV/r, possibly driven by a diminished perceived need for empiric antibiotic therapy. Treatment with NMV/r may reduce unnecessary outpatient antibiotic use. Antibiotics should be reserved for patients with a high suspicion of bacterial co-infection.IMPORTANCEAntimicrobial resistance, driven by the overuse of antibiotics, is a major global health threat. The coronavirus disease 2019 (COVID-19) pandemic has complicated this issue, with antibiotics often prescribed to patients with COVID-19 despite being ineffective against viruses. These practices, typically aimed at preventing or empirically treating rare bacterial co-infections, have raised concerns about accelerating resistance. The antiviral nirmatrelvir/ritonavir (NMV/r), widely used in high-risk patients with COVID-19 to prevent severe illness, offers an opportunity to reassess antibiotic use in patients with respiratory infections. Our study of over 300,000 patients in a national healthcare system found that those treated with NMV/r for COVID-19 were 35% less likely to receive antibiotics than those who did not receive the antiviral. Lower antibiotic use among patients treated with NMV/r may reflect a reduction in unnecessary outpatient antibiotic use. These findings highlight the potential role of antivirals in supporting antibiotic stewardship and addressing a critical public health challenge.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0320924"},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557416","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":"Deciphering the role of SMU.1147 in peptide-mediated signaling and competence in <i>Streptococcus mutans</i>.","authors":"Jeong Nam Kim, Si-Uk Ryoo, Yeuna Nam","doi":"10.1128/spectrum.02917-24","DOIUrl":"10.1128/spectrum.02917-24","url":null,"abstract":"<p><p><i>Streptococcus mutans</i> is a primary cariogenic pathogen involved in dental biofilm formation, a major virulence factor in the development of dental caries. In <i>S. mutans</i>, the competence-stimulating peptide (CSP), encoded by <i>comC</i>, plays a critical role in environmental stress response, growth regulation, and virulence expression. In this study, we performed transcriptome analysis to investigate the role of SMU.1147, a unique core gene in <i>S. mutans</i>, in biological pathways related to transport, defense responses, and environmental sensing. The deletion of SMU.1147 led to the upregulation of genes involved in carbohydrate uptake and metabolism, particularly phosphotransferase system (PTS) transporters, thereby enhancing the sugar transport capacity. However, despite increased sugar uptake, the mutant strain did not show significant changes in growth rate or ATP production and displayed slightly reduced organic acid production. Additionally, the mutant exhibited significantly reduced cell viability after an 8-h incubation compared to the parental strain. Notably, genes associated with CSP-dependent signal transduction and stress defense, such as <i>comX</i>, <i>comR</i>, <i>htrA</i>, <i>scnRK</i>, and <i>ciaRH</i>, were downregulated in the mutant strain. Furthermore, stress-related genes, including <i>spxA2</i>, <i>clpP</i>, and <i>clpX</i>, were significantly downregulated, suggesting compromised protein quality control and oxidative stress responses. Our findings suggest that SMU.1147 plays a critical role in regulating peptide-mediated signaling, metabolic coordination, and environmental adaptation in <i>S. mutans</i>, positioning it as a key integrator of the metabolic and stress response networks that are essential for pathogenicity and survival.</p><p><strong>Importance: </strong>Understanding the regulatory mechanisms that govern virulence and environmental adaptation in <i>Streptococcus mutans</i> is essential for developing strategies to mitigate dental caries. This study reveals the critical role of the SMU.1147 gene in <i>S. mutans</i> in metabolic regulation, stress response, and cell viability. Our results demonstrate how the deletion of this gene affects sugar uptake and organic acid production, leading to imbalances in carbon metabolism and reduced long-term survival. These findings provide valuable insights into the ability of <i>S. mutans</i> to adapt to stressed conditions and highlight the role of SMU.1147 in modulating biofilm formation and virulence, contributing to our understanding of regulatory pathways in dental pathogens.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0291724"},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557433","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":"Multi-omics analysis of the mechanism of alfalfa and wheat-induced rumen flatulence in Xizang sheep.","authors":"Jing Wu, Xiaoming Zhang, Khan Ayesha, Shahzad Khuram, Jianzhao Cui, Gaofu Wang, Zhaxi Yangzong, Mingyan Shi, Xunping Jiang, Long Li, Guiqiong Liu, Wangsheng Zhao, Tianzeng Song","doi":"10.1128/spectrum.03268-24","DOIUrl":"10.1128/spectrum.03268-24","url":null,"abstract":"<p><p>Rumen flatulence is a diet-related rumen disease in ruminants. This study induced a rumen flatulence model in Xizang sheep using alfalfa (HRF) and wheatgrass (MRF). The aim was to understand the rumen microbiota diversity in healthy and pathological states, host-microbiota interactions, and the molecular mechanisms of rumen flatulence. Results showed that the pH in the HRF and MRF groups was lower than that in the natural grass group (LRF). SCFA concentrations varied between groups: in HRF, 2-BA and CA increased; in MRF, 4-MVA and 5-MCA rose. Microbial analysis indicated that the alpha- and beta-diversity of HRF and MRF groups were lower than LRF's, with different microbial compositions. Transcriptome analysis revealed many differentially expressed genes (DEGs). Compared to MRF, HRF had 348 upregulated and 511 downregulated DEGs. Versus LRF, MRF had 201 upregulated and 185 downregulated DEGs, while HRF had 128 upregulated and 238 downregulated DEGs. Spearman's correlation analysis showed that there was a positive correlation between <i>Butyrivibrio</i>, <i>Quinella,</i> and specific genes. These findings reveal the potential mechanism of rumen flatulence in Xizang sheep and provide new insights into the prevention and treatment of the disease.IMPORTANCEThe research used a high-protein diet to induce a model to understand the diversity of rumen microbiota and its interaction with the host, as well as exploring the molecular mechanisms of rumen flatulence.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0326824"},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573469","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":"Unveiling novel features and phylogenomic assessment of indigenous <i>Priestia megaterium</i> AB-S79 using comparative genomics.","authors":"Adetomiwa Ayodele Adeniji, Chinenyenwa Fortune Chukwuneme, Emilyn Costa Conceição, Ayansina Segun Ayangbenro, Eduan Wilkinson, Elizna Maasdorp, Tulio de Oliveira, Olubukola Oluranti Babalola","doi":"10.1128/spectrum.01466-24","DOIUrl":"10.1128/spectrum.01466-24","url":null,"abstract":"<p><p><i>Priestia megaterium</i> strain AB-S79 isolated from active gold mine soil previously expressed <i>in vitro</i> heavy metal resistance and has a 5.7 Mb genome useful for biotechnological exploitation. This study used web-based bioinformatic resources to analyze <i>P. megaterium</i> AB-S79 genomic relatedness, decipher its secondary metabolite biosynthetic gene clusters (BGCs), and better comprehend its taxa. Genes were highly conserved across the 14 <i>P</i>. <i>megaterium</i> genomes examined here. The pangenome reflected a total of 61,397 protein-coding genes, 59,745 homolog protein family hits, and 1,652 singleton protein family hits. There were also 7,735 protein families, including 1,653 singleton families and 6,082 homolog families. OrthoVenn3 comparison of AB-S79 protein sequences with 13 other <i>P. megaterium</i> strains, 7 other <i>Priestia</i> spp., and 6 other <i>Bacillus</i> spp. highlighted AB-S79's unique genomic and evolutionary trait. antiSMASH identified two key transcription factor binding site regulators in AB-S79's genome: zinc-responsive repressor (Zur) and antibiotic production activator (AbrC3), plus putative enzymes for the biosynthesis of terpenes and ranthipeptides. AB-S79 also harbors BGCs for two unique siderophores (synechobactins and schizokinens), phosphonate, dienelactone hydrolase family protein, and phenazine biosynthesis protein (phzF), which is significant for this study. Phosphonate particularly showed specificity for the <i>P. megaterium</i> sp. validating the effect of gene family expansion and contraction. <i>P. megaterium</i> AB-S79 looks to be a viable source for value-added compounds. Thus, this study contributes to the theoretical framework for the systematic metabolic and genetic exploitation of the <i>P. megaterium</i> sp., particularly the value-yielding strains.</p><p><strong>Importance: </strong>This study explores microbial natural product discovery using genome mining, focusing on <i>Priestia megaterium</i>. Key findings highlight the potential of <i>P. megaterium</i>, particularly strain AB-S79, for biotechnological applications. The research shows a limited output of <i>P. megaterium</i> genome sequences from Africa, emphasizing the importance of the native strain AB-S79. Additionally, the study underlines the strain's diverse metabolic capabilities, reinforcing its suitability as a model for microbial cell factories and its foundational role in future biotechnological exploitation.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0146624"},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449496","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":"Very preterm gut microbiota development from the first week of life to 3.5 years of age: a prospective longitudinal multicenter study.","authors":"Gaël Toubon, Constance Patin, Johanne Delannoy, Jean-Christophe Rozé, Frédéric Barbut, Pierre-Yves Ancel, Marie-Aline Charles, Marie-José Butel, Patricia Lepage, Julio Aires","doi":"10.1128/spectrum.01636-24","DOIUrl":"10.1128/spectrum.01636-24","url":null,"abstract":"<p><p>This study analyzed the longitudinal evolution of intestinal microbiota in very preterm neonates (PN) during and after their hospitalization. The bacterial 16S rRNA gene sequencing approach was applied for the analysis of fecal samples (<i>n</i> = 1,307) from 596 PN. Samples were collected at one week after birth, at one month, at the neonatal intensive care unit discharge, and at 3.5 years of age. Over time, the intestinal microbiota of the infants matured progressively, with increasing alpha diversity and decreasing beta diversity. Based on a Dirichlet multinomial mixture clustering approach (DMM), during hospitalization, infants progressed among ten different clusters. At 3.5 years of age, only three clusters were identified. The influence of the gestational age, the neonatal antibiotic administration, and the maternal antibiotic therapy during delivery on the gut microbiota varied over time and depended on the sampling period. Preconceptional maternal body mass index (BMI) was associated with the gut microbiota of infants during the hospitalization period and at 3.5 years of age. Infants with a lower gestational age or those born by Cesarean section shifted between clusters more frequently. Using PICRUSt2, the inferred metabolic pathways revealed a change in the functional capacities of the intestinal microbiota over time. We found that preconceptional maternal BMI was the only consistent perinatal factor influencing the development of the gut microbiota over time. After hospital discharge, infants exhibited a transition toward a microbiota community similar to that of adults by 3.5 years of age, in accordance with the functional metabolic pathways of the gut microbiota.IMPORTANCEThis study is among the very few reports analyzing the gut microbiota development in very preterm infants over time in a large, multicenter population of 596 children from a well-described nationwide birth cohort, with a follow-up until the age of 3.5 years. The maturation of the intestinal microbiota was confirmed to occur over time, with increased alpha diversity and decreased beta diversity. Specifically, 13 microbiota clusters were identified during the hospitalization period, while and only three clusters were observed at 3.5 years. Infants born prematurely or via Cesarean section exhibited a less stable microbiota, frequently shifting clusters. A number of perinatal factors were identified as influencing the development of the microbiota. Among these, the preconceptional maternal BMI emerged as the only consistent factor up to 3.5 years. The metabolic pathways of the microbiota evolved over time, in accordance with the maturation of the gut microbiota.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0163624"},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449509","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":"Effects of human immunoglobulin A on <i>Cryptococcus neoformans</i> morphology and gene expression.","authors":"Nuria Trevijano-Contador, Haroldo C de Oliveira, Claudia Malacatus-Bravo, Varona Sarai, Isabel Cuesta, Marcio L Rodrigues, Óscar Zaragoza, Liise-Anne Pirofski","doi":"10.1128/spectrum.02008-24","DOIUrl":"10.1128/spectrum.02008-24","url":null,"abstract":"<p><p>Human IgM was previously shown to inhibit Titan-like cell formation of <i>Cryptococcus neoformans</i>, whereas IgG did not. Here, we conducted an in-depth analysis of the effect of normal human IgA on <i>C. neoformans</i> biology (strain H99) and compared it to that of IgG and IgM. We found that like IgM, IgA affected H99 cell size and morphology. The total size of cells cultured with IgA was significantly smaller at 24 h than cells cultured with IgM and IgG and comparable to IgM but smaller than IgG at 72 h. We also examined extracellular vesicle (EV) production and found that it was significantly reduced in cells cultured with IgA than the control, but the EVs were larger. To further probe the effect of IgA on H99, we performed expression profiling by RNAseq of H99 cells cultured with each immunoglobulin isotype and compared the results with IgA to those with IgM, IgG, and a control (PBS). These comparisons showed that cells cultured with IgA overexpressed genes related to cell rescue, defense, virulence, energy conservation, adapation to stress with CNAG_00735 (aldehyde dehydrogenase family seven member A1) being the most overexpressed, and repressed some genes related to vesicular transport, including CNAG_04306 (vesicle transporter SFT2B) and CNG_00063 (histone H3). Collectively, our findings suggest that the effects of IgA on cryptococcal biology deserve further investigation, as they reveal new insights into human host-<i>C. neoformans</i> interaction, which suggest that antibody responses may affect gene expression in <i>C. neoformans</i>.IMPORTANCEProfound CD4 T cell deficiency is associated with the development of cryptococcosis in HIV-infected individuals. However, perturbations in antibody immunity, including reduced levels of plasma IgA and IgM, have also been associated with cryptococcal disease status. While IgM has been studied in some detail, IgA has not. Here, we evaluated the effect of normal human IgA on <i>Cryptococcus neoformans</i> biology and morphology to expand knowledge of the role that it may play in cryptococcal pathogenesis.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0200824"},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468396","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":"<i>In vitro</i> assays for clinical isolates of sequence type 131 <i>Escherichia coli</i> do not recapitulate <i>in vivo</i> infectivity using a murine model of urinary tract infection.","authors":"Courtney P Rudick, Rachel S Cox, Travis J Bourret, Nancy D Hanson","doi":"10.1128/spectrum.01511-24","DOIUrl":"10.1128/spectrum.01511-24","url":null,"abstract":"<p><p>Sequence type 131 isolates are a major cause of cystitis and pyelonephritis. Many studies rely solely on <i>in vitro</i> assays to screen for bacterial virulence factors associated with the pathogenicity of clinical isolates of <i>Escherichia coli</i>. Few studies have compared <i>in vitro</i> findings with <i>in vivo</i> infectivity of clinical isolates. The purpose of this study was to evaluate the correlation between <i>in vitro</i> assays with the ability to cause cystitis and pyelonephritis in a murine model of urinary tract infection. <i>In vitro</i> assays were conducted according to the published protocols and included motility assays, biofilm formation, epithelial cell adhesion and invasion, and curli production. Twenty-one uropathogenic <i>E. coli</i> (UPEC) isolates of <i>E. coli</i> ST131 and non-ST131 were used for both <i>in vivo</i> and <i>in vitro</i> studies. Six mice per isolate were inoculated via urethral catheterization. Colony forming units (CFUs) were determined from bladder and kidneys. <i>In vitro</i> and <i>in vivo</i> correlations were evaluated by multiple linear regression analysis. Pairwise linear regressions showed trendlines with weak positive correlations for motility, adhesion, and invasion and weak negative correlations for hemagglutination, biofilm, and curli production. The ability of <i>E. coli</i> ST131 and non-ST131 clinical isolates to cause cystitis and pyelonephritis varied among strains. The <i>R</i>² Pearson correlation value was less than ±0.5 for any pair, indicating little to no statistical association between <i>in vitro</i> and <i>in vivo</i> findings. These data show that <i>in vitro</i> data are not predictive of the ability of ST131 <i>E. coli</i> to infect and/or cause disease in a mouse model.</p><p><strong>Importance: </strong>Urinary tract infections (UTIs) affect 150 million people annually, and <i>E. coli</i> ST131, a pandemic clone, has become responsible for a significant portion of those UTIs. How ST131 <i>E. coli</i> has become such a successful strain remains to be elucidated. When evaluating bacterial pathogenicity, it is customary to use <i>in vitro</i> assays to predict isolate virulence and fitness due to lower cost and ease of experimentation compared with <i>in vivo</i> models. It is common to use model organisms like pathogenic <i>E. coli</i> CFT073 or a non-pathogenic K12 lab strain as representatives for the entire species. However, our research has shown that model organisms differ from ST131 <i>E. coli,</i> and <i>in vitro</i> assays are poor predictors of ST131 isolate infectivity in a murine model of UTI. As such, research into the mechanisms of fitness/pathogenesis for ST131 infectivity needs to focus on these organisms rather than other types of UPEC.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0151124"},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492943","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":"ZntR is a critical regulator for zinc homeostasis and involved in pathogenicity in <i>Riemerella anatipestifer</i>.","authors":"Hongmeng Ma, Mengying Wang, Yizhou Yao, Shutong Zhang, Mingshu Wang, Dekang Zhu, Renyong Jia, Shun Chen, Xinxin Zhao, Qiao Yang, Ying Wu, Shaqiu Zhang, Juan Huang, Bin Tian, Xumin Ou, Di Sun, Yu He, Zhen Wu, Ling Zhang, Yanling Yu, Anchun Cheng, Mafeng Liu","doi":"10.1128/spectrum.03178-24","DOIUrl":"10.1128/spectrum.03178-24","url":null,"abstract":"<p><p>Zinc (Zn²⁺) is essential for all bacteria, but excessive Zn²⁺ levels are toxic. Bacteria maintain zinc homeostasis through regulators, such as Zur, AdcR, and ZntR. <i>Riemerella anatipestifer</i> is a significant <i>Flavobacteriales</i> pathogen causing acute serositis in ducks and other birds. In this study, we identified a homolog of ZntR, a regulator for zinc homeostasis, and demonstrated its contribution to the pathogenicity of <i>R. anatipestifer</i>. Deletion of <i>zntR</i> makes the bacteria hypersensitive to excess Zn²⁺ but not to other metals like manganese (Mn²⁺), copper (Cu²⁺), cobalt (Co²⁺), and nickel (Ni²⁺). Deletion of <i>zntR</i> also leads to intracellular zinc accumulation but not of other metals. Additionally, compared to the wild type, the deletion of <i>zntR</i> increases resistance to oxidants hydrogen peroxide (H₂O₂) and sodium hypochlorite (NaOCl), respectively. The deletion of <i>zntR</i> causes significant changes in transcriptional and protein expression levels, revealing 35 genes with potential zinc metabolism functions. Among them, <i>zupT</i>, which is inhibited by ZntR, is required for zinc transport and resistance to oxidative stress. Finally, deletion of <i>zntR</i> leads to attenuation of colonization in ducklings. In summary, ZntR is a crucial regulator for zinc homeostasis and contributes to the pathogenicity of <i>R. anatipestifer</i>.IMPORTANCEZinc homeostasis plays a critical role in the environmental adaptability of bacteria. <i>Riemerella anatipestifer</i> is a significant pathogen in poultry with the potential to encounter zinc-deficient or zinc-excess environment. The mechanism of zinc homeostasis in this bacterium remains largely unexplored. In this study, we showed that the transcriptional regulator ZntR of <i>R. anatipestifer</i> is critical for zinc homeostasis by altering the transcription and expression of a number of genes. Importantly, ZntR inhibits the transcription of zinc transporter ZupT and contributes to colonization in <i>R. anatipestifer</i>. The results are significant for understanding zinc homeostasis and the pathogenic mechanisms in <i>R. anatipestifer</i>.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0317824"},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542548","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":"Epidemiological characteristics and antimicrobial resistance of extensively drug-resistant <i>Acinetobacter baumannii</i> in ICU wards.","authors":"Jingchao Shi, Xiaoting Mao, Fengtian Sun, Jianghao Cheng, Lijia Shao, Xiaoyun Shan, Yijun Zhu","doi":"10.1128/spectrum.02619-24","DOIUrl":"10.1128/spectrum.02619-24","url":null,"abstract":"<p><p><i>Acinetobacter baumannii</i> is a significant nosocomial pathogen, particularly problematic due to its extensive drug resistance. This study investigates 56 extensively drug-resistant <i>A. baumannii</i> (XDRAB) strains collected from various ICU wards at Jinhua Central Hospital, Zhejiang Province, China. Strains were isolated from diverse clinical samples, including sputum, blood, cerebrospinal fluid, and wound secretions. Identification was confirmed via matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), and antibiotic susceptibility testing was conducted using the VITEK 2 Compact system, E-test, and Kirby-Bauer methods. All strains were susceptible to polymyxin, with four showing intermediate susceptibility to tigecycline, while resistance rates to other antibiotics were 100%. Molecular typing through pulsed-field gel electrophoresis (PFGE) classified the strains into 10 types, with the dominant type (G) primarily found in ICU3, indicating a potential clonal outbreak. Whole-genome sequencing (WGS) and multi-locus sequence typing (MLST) identified ST208 as the predominant sequence type. Resistance gene screening revealed the presence of blaOXA-23, blaTEM-1D, and aminoglycoside resistance genes in most strains. Phylogenetic analysis confirmed the clonal transmission of ST208 strains across the hospital, with a high degree of genomic similarity among the isolates. These findings highlight the importance of continuous monitoring and effective infection control measures to prevent the spread of XDRAB in healthcare settings.IMPORTANCEExtensively drug-resistant <i>Acinetobacter baumannii</i> is a critical public health threat, particularly in hospital environments where it causes a variety of infections. The global spread of extensively drug-resistant <i>A. baumannii</i> (XDRAB) and its resistance to most antibiotics make treatment options limited, increasing the risk of patient morbidity and mortality. This study provides important insights into the molecular epidemiology of XDRAB in a hospital setting, revealing the clonal transmission of the ST208 sequence type. By utilizing both pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS), we identified genetic links between strains and the presence of key resistance genes. The findings underscore the urgent need for robust infection control protocols, routine surveillance, and judicious use of antibiotics to mitigate the spread of XDRAB and ensure better patient outcomes.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0261924"},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542561","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}