Oliver J Hills, Isaac O K Noble, Alex Heyam, Andrew J Scott, James Smith, Helen F Chappell
{"title":"Atomistic modelling and NMR studies reveal that gallium can target the ferric PQS uptake system in <i>P. aeruginosa</i> biofilms.","authors":"Oliver J Hills, Isaac O K Noble, Alex Heyam, Andrew J Scott, James Smith, Helen F Chappell","doi":"10.1099/mic.0.001422","DOIUrl":"10.1099/mic.0.001422","url":null,"abstract":"<p><p>Intravenous gallium nitrate therapy is a novel therapeutic strategy deployed to combat chronic <i>Pseudomonas aeruginosa</i> biofilm infections in the lungs of cystic fibrosis (CF) patients by interfering with iron (Fe<sup>3+</sup>) uptake. The therapy is a source of Ga<sup>3+</sup>, which competes with Fe<sup>3+</sup> for siderophore binding, subsequently disrupting iron metabolism and inhibiting biofilm proliferation <i>in vivo</i>. It was recently demonstrated that the <i>Pseudomonas</i> quinolone signal (PQS) can chelate Fe<sup>3+</sup> to assist in bacterial iron uptake. However, it is unknown whether exogenous gallium also targets [Fe(PQS)<sub>3</sub>] uptake, which, in turn, would extend the mechanism of gallium therapy beyond siderophore competition, potentially supporting use of the therapy against <i>P. aeruginosa</i> mutants deficient in siderophore uptake proteins. To that end, the thermodynamic feasibility of iron-for-gallium cation exchange into [Fe(PQS)<sub>3</sub>] was evaluated using quantum chemical density functional theory (DFT) modelling and verified experimentally using <sup>1</sup>H nuclear magnetic resonance (NMR). We demonstrate here that Ga<sup>3+</sup> can strongly bind to three PQS molecules and, furthermore, displace and substitute Fe<sup>3+</sup> from the native chelate pocket within PQS complexes, through a Trojan horse mechanism, retaining the key structural features present within the native ferric complex. As such, [Fe(PQS)<sub>3</sub>] complexes, in addition to ferric-siderophore complexes, represent another target for gallium therapy.</p>","PeriodicalId":49819,"journal":{"name":"Microbiology-Sgm","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10765035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138806790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Interbacterial competition mediated by the type VIIb secretion system.","authors":"Eleanor R Boardman, Tracy Palmer, Felicity Alcock","doi":"10.1099/mic.0.001420","DOIUrl":"10.1099/mic.0.001420","url":null,"abstract":"<p><p>Successful occupancy of a given niche requires the colonising bacteria to interact extensively with the biotic and abiotic environment, including other resident microbes. Bacteria have evolved a range of protein secretion machines for this purpose with eleven such systems identified to date. The type VIIb secretion system (T7SSb) is utilised by Bacillota to secrete a range of protein substrates, including antibacterial toxins targeting closely related strains, and the system as a whole has been implicated in a range of activities such as iron acquisition, intercellular signalling, host colonisation and virulence. This review covers the components and secretion mechanism of the T7SSb, the substrates of these systems and their roles in Gram-positive bacteria, with a focus on interbacterial competition.</p>","PeriodicalId":49819,"journal":{"name":"Microbiology-Sgm","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10765036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138806807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jessica M Ochoa, Philip Dershwitz, Mary Schappert, Sharmistha Sinha, Taylor I Herring, Todd O Yeates, Thomas A Bobik
{"title":"A single shell protein plays a major role in choline transport across the shell of the choline utilization microcompartment of <i>Escherichia coli</i> 536.","authors":"Jessica M Ochoa, Philip Dershwitz, Mary Schappert, Sharmistha Sinha, Taylor I Herring, Todd O Yeates, Thomas A Bobik","doi":"10.1099/mic.0.001413","DOIUrl":"10.1099/mic.0.001413","url":null,"abstract":"<p><p>Bacterial microcompartments (MCPs) are widespread protein-based organelles that play important roles in the global carbon cycle and in the physiology of diverse bacteria, including a number of pathogens. MCPs consist of metabolic enzymes encapsulated within a protein shell. The main roles of MCPs are to concentrate enzymes together with their substrates (to increase reaction rates) and to sequester harmful metabolic intermediates. Prior studies indicate that MCPs have a selectively permeable protein shell, but the mechanisms that allow selective transport across the shell are not fully understood. Here we examine transport across the shell of the choline utilization (Cut) MCP of <i>Escherichia coli</i> 536, which has not been studied before. The shell of the Cut MCP is unusual in consisting of one pentameric and four hexameric bacterial microcompartment (BMC) domain proteins. It lacks trimeric shell proteins, which are thought to be required for the transport of larger substrates and enzymatic cofactors. In addition, its four hexameric BMC domain proteins are very similar in amino acid sequence. This raises questions about how the Cut MCP mediates the selective transport of the substrate, products and cofactors of choline metabolism. In this report, site-directed mutagenesis is used to modify the central pores (the main transport channels) of all four Cut BMC hexamers to assess their transport roles. Our findings indicate that a single shell protein, CmcB, plays the major role in choline transport across the shell of the Cut MCP and that the electrostatic properties of the CmcB pore also impact choline transport. The implications of these findings with regard to the higher-order structure of MCPs are discussed.</p>","PeriodicalId":49819,"journal":{"name":"Microbiology-Sgm","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10710832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136400050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joanna Urbaniec, Maria Getino, Tahnee B-D McEwan, Martina L Sanderson-Smith, Johnjoe McFadden, Faisal Hai, Roberto La Ragione, Marwa M Hassan, Suzie Hingley-Wilson
{"title":"Anti-persister efficacy of colistin and meropenem against uropathogenic <i>Escherichia coli</i> is dependent on environmental conditions.","authors":"Joanna Urbaniec, Maria Getino, Tahnee B-D McEwan, Martina L Sanderson-Smith, Johnjoe McFadden, Faisal Hai, Roberto La Ragione, Marwa M Hassan, Suzie Hingley-Wilson","doi":"10.1099/mic.0.001403","DOIUrl":"10.1099/mic.0.001403","url":null,"abstract":"<p><p>Antibiotic persistence is a phenomenon observed when genetically susceptible cells survive long-term exposure to antibiotics. These 'persisters' are an intrinsic component of bacterial populations and stem from phenotypic heterogeneity. Persistence to antibiotics is a concern for public health globally, as it increases treatment duration and can contribute to treatment failure. Furthermore, there is a growing array of evidence that persistence is a 'stepping-stone' for the development of genetic antimicrobial resistance. Urinary tract infections (UTIs) are a major contributor to antibiotic consumption worldwide, and are known to be both persistent (i.e. affecting the host for a prolonged period) and recurring. Currently, in clinical settings, routine laboratory screening of pathogenic isolates does not determine the presence or the frequency of persister cells. Furthermore, the majority of research undertaken on antibiotic persistence has been done on lab-adapted bacterial strains. In the study presented here, we characterized antibiotic persisters in a panel of clinical uropathogenic <i>Escherichia coli</i> isolates collected from hospitals in the UK and Australia. We found that a urine-pH mimicking environment not only induces higher levels of antibiotic persistence to meropenem and colistin than standard laboratory growth conditions, but also results in rapid development of transient colistin resistance, regardless of the genetic resistance profile of the isolate. Furthermore, we provide evidence for the presence of multiple virulence factors involved in stress resistance and biofilm formation in the genomes of these isolates, whose activities have been previously shown to contribute to the formation of persister cells.</p>","PeriodicalId":49819,"journal":{"name":"Microbiology-Sgm","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10710840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138292265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vittorio Venturi, Mihael Špacapan, Nemanja Ristović, Cristina Bez
{"title":"RsaM: a unique dominant regulator of AHL quorum sensing in bacteria.","authors":"Vittorio Venturi, Mihael Špacapan, Nemanja Ristović, Cristina Bez","doi":"10.1099/mic.0.001417","DOIUrl":"10.1099/mic.0.001417","url":null,"abstract":"<p><p>Quorum sensing (QS) in proteobacteria is a mechanism to control gene expression orchestrated by the LuxI/LuxR protein family pair, which produces and responds to <i>N</i>-acyl homoserine lactone (AHL) diffusible signal molecules. QS is often regarded as a cell density response via the sensing of/response to the concentrations of AHLs, which are constantly basally produced by bacterial cells. The <i>luxI/R</i> systems, however, undergo supra-regulation in response to external stimuli and many regulators have been implicated in controlling QS in bacteria, although it remains unclear how most of these regulators and cues contribute to the QS response. One regulator, called RsaM, has been reported in a few proteobacterial species to have a stringent role in the control of AHL QS. RsaMs are small, in the range of 140-170 aa long, and are found in several genera, principally in <i>Burkholderia</i> and <i>Acinetobacter</i>. The gene encoding RsaM is always located as an independent transcriptional unit, situated adjacent to QS <i>luxI</i> and/or <i>luxR</i> loci. One of the most remarkable aspects of RsaM is its uniqueness; it does not fall into any of the known bacterial regulatory families and it possesses a distinct and novel fold that does not exhibit binding affinity for nucleic acids or AHLs. RsaM stands out as a distinctive regulator in bacteria, as it is likely to have an important ecological role, as well as unravelling a novel way of gene regulation in bacteria.</p>","PeriodicalId":49819,"journal":{"name":"Microbiology-Sgm","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10710839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138446793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Taoran Fu, Danna R Gifford, Christopher G Knight, Michael A Brockhurst
{"title":"Eco-evolutionary dynamics of experimental <i>Pseudomonas aeruginosa</i> populations under oxidative stress.","authors":"Taoran Fu, Danna R Gifford, Christopher G Knight, Michael A Brockhurst","doi":"10.1099/mic.0.001396","DOIUrl":"10.1099/mic.0.001396","url":null,"abstract":"","PeriodicalId":49819,"journal":{"name":"Microbiology-Sgm","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10710836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71523201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Isolation, characterization and screening of actinomycetes associated with fijian ant-plant symbioses.","authors":"Umar Diarra, Tamara Osborne-Naikatini","doi":"10.1099/mic.0.001410","DOIUrl":"10.1099/mic.0.001410","url":null,"abstract":"<p><p>In the search for novel therapeutics to combat the ongoing antimicrobial resistance crisis, scientists are turning to underexplored environments. Defensive mutualisms between hymenopteran insects and actinomycetes represent important reservoirs for bioactive compounds. In this study, we examined the association between actinomycetes and <i>Squamellaria</i> ant-plants spanning three different ant and plant species combinations (<i>Squamellaria imberbis-Philidris nagasau, Squamellaria tenuiflora- Technomyrmex vitiensis</i>, and <i>Squamellaria tenuiflora-Tetramorium insolens</i>). Eight <i>Squamellaria</i> plants were sampled including four containing <i>T. vitiensis,</i> three containing <i>P. nagasau,</i> and a single plant containing <i>T. insolens</i>. A total of 47 actinomycetes were obtained from the sampled material, with 5, 16, and 26 isolates originating from cuticle, tissue, and nest samples, respectively. Cross-streaking tests showed that 12 out of 47 isolates inhibited bacterial pathogens. The most frequently inhibited pathogens in the cross-streaking tests were <i>S. aureus</i> and <i>E. coli</i> while <i>S. enterica</i> was the least inhibited. Among the three primary screening media used, ISP2 agar was the most suitable for secondary metabolism as more isolates exhibited antibacterial activity when grown on the medium. TFS2010 and TFS2003, which matched to <i>Streptomyces gramineus</i> (>99% similarity), were the most bioactive isolates in cross-streaking tests. TFS2010 displayed the strong antibacterial on Nutrient agar, Mueller Hinton agar, and ISP2 agar while TFS2003 only exhibited strong antibacterial activity on Nutrient agar. Furthermore, a difference in potency of extracts based on batch culture medium was noted in TFS2010<b>.</b> DNA was extracted from 19 isolates and followed by 16SrRNA gene sequencing. Analysis of sequence data revealed the presence of six genera, including <i>Amycolatopsis</i>, <i>Asanoa</i>, <i>Jiangella</i>, <i>Nocardia</i>, <i>Nocardiopsis</i>, and <i>Streptomyces</i>, with the latter being the most abundant taxon. Among these, three isolates (PNS3002, PNS3005, and TFS3001) are likely to represent new species while one (TFS2015) is likely to be a member of a novel genus. Our work represents the first attempt to study actinomycetes from <i>Squamellaria</i>-ant mutualisms.</p>","PeriodicalId":49819,"journal":{"name":"Microbiology-Sgm","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10710841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71523202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<i>Clostridioides difficile</i> spores tolerate disinfection with sodium hypochlorite disinfectant and remain viable within surgical scrubs and gown fabrics.","authors":"Humaira Ahmed, Lovleen Tina Joshi","doi":"10.1099/mic.0.001418","DOIUrl":"10.1099/mic.0.001418","url":null,"abstract":"","PeriodicalId":49819,"journal":{"name":"Microbiology-Sgm","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10710845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138292264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Microbe Profile: <i>Ehrlichia ruminantium</i> - stealthy as it goes.","authors":"Damien F Meyer, Amal Moumène, Valérie Rodrigues","doi":"10.1099/mic.0.001415","DOIUrl":"10.1099/mic.0.001415","url":null,"abstract":"","PeriodicalId":49819,"journal":{"name":"Microbiology-Sgm","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10710844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138296300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stephany Navarro, Habib Abla, Jane A Colmer-Hamood, Gary Ventolini, Abdul N Hamood
{"title":"Under conditions closely mimicking vaginal fluid, <i>Lactobacillus jensenii</i> strain 62B produces a bacteriocin-like inhibitory substance that targets and eliminates <i>Gardnerella</i> species.","authors":"Stephany Navarro, Habib Abla, Jane A Colmer-Hamood, Gary Ventolini, Abdul N Hamood","doi":"10.1099/mic.0.001409","DOIUrl":"10.1099/mic.0.001409","url":null,"abstract":"<p><p>Within the vaginal ecosystem, lactobacilli and <i>Gardnerella</i> spp. likely interact and influence each other's growth, yet the details of this interaction are not clearly defined. Using medium simulating vaginal fluid and a two-chamber co-culturing system to prevent cell-to-cell contact between the bacteria, we examined the possibility that <i>Lactobacillus jensenii</i> 62B (Lj 62B) and/or <i>G. piotii</i> (Gp) JCP8151B produce extracellular factors through which they influence each other's viability. By 24 h post-inoculation (hpi) in the co-culture system and under conditions similar to the vaginal environment - pH 5.0, 37 °C, and 5% CO<sub>2</sub>, Lj 62B viability was not affected but Gp JCP8151B had been eliminated. Cell-free supernatant harvested from Lj 62B cultures (Lj-CFS) at 20 hpi, but not 16 hpi, also eliminated Gp JCP8151B growth. Neither lactic acid nor H<sub>2</sub>O<sub>2</sub> production by Lj 62B was responsible for this effect. The Lj-CFS did not affect viability of three species of lactobacilli or eight species of Gram-positive and Gram-negative uropathogens but eliminated viability of eight different strains of <i>Gardnerella</i> spp. Activity of the inhibitory factor within Lj-CFS was abolished by protease treatment and reduced by heat treatment suggesting it is most likely a bacteriocin-like protein; fractionation revealed that the factor has a molecular weight within the 10-30 kDa range. These results suggest that, in medium mimicking vaginal fluid and growth conditions similar to the vaginal environment, Lj 62B produces a potential bacteriocin-like inhibitory substance (Lj-BLIS) that clearly targets <i>Gardnerella</i> spp. strains. Once fully characterized, Lj-BLIS may be a potential treatment for <i>Gardnerella-</i>related BV that does not alter the vaginal microflora.</p>","PeriodicalId":49819,"journal":{"name":"Microbiology-Sgm","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10710834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71428437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}