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  • 1
    Online Resource
    Online Resource
    Extensive remodelling of the cell wall during the development of Staphylococcus aureus bacteraemia
    eLife Sciences Publications, Ltd ; 2023
    In:  eLife Vol. 12 ( 2023-07-04)
    Details
    In: eLife, eLife Sciences Publications, Ltd, Vol. 12 ( 2023-07-04)
    Abstract: The bloodstream represents a hostile environment that bacteria must overcome to cause bacteraemia. To understand how the major human pathogen Staphylococcus aureus manages this we have utilised a functional genomics approach to identify a number of new loci that affect the ability of the bacteria to survive exposure to serum, the critical first step in the development of bacteraemia. The expression of one of these genes, tcaA, was found to be induced upon exposure to serum, and we show that it is involved in the elaboration of a critical virulence factor, the wall teichoic acids (WTA), within the cell envelope. The activity of the TcaA protein alters the sensitivity of the bacteria to cell wall attacking agents, including antimicrobial peptides, human defence fatty acids, and several antibiotics. This protein also affects the autolytic activity and lysostaphin sensitivity of the bacteria, suggesting that in addition to changing WTA abundance in the cell envelope, it also plays a role in peptidoglycan crosslinking. With TcaA rendering the bacteria more susceptible to serum killing, while simultaneously increasing the abundance of WTA in the cell envelope, it was unclear what effect this protein may have during infection. To explore this, we examined human data and performed murine experimental infections. Collectively, our data suggests that whilst mutations in tcaA are selected for during bacteraemia, this protein positively contributes to the virulence of S. aureus through its involvement in altering the cell wall architecture of the bacteria, a process that appears to play a key role in the development of bacteraemia.
    Type of Medium: Online Resource
    ISSN: 2050-084X
    URL: Article
    DOI: 10.7554/eLife.87026.3
    Language: English
    Publisher: eLife Sciences Publications, Ltd
    Publication Date: 2023
    detail.hit.zdb_id: 2687154-3
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  • 2
    Online Resource
    Online Resource
    The MpsB protein contributes to both the toxicity and immune evasion capacity of Staphylococcus aureus
    Microbiology Society ; 2021
    In:  Microbiology Vol. 167, No. 10 ( 2021-10-07)
    Details
    In: Microbiology, Microbiology Society, Vol. 167, No. 10 ( 2021-10-07)
    Abstract: Understanding the role specific bacterial factors play in the development of severe disease in humans is critical if new approaches to tackle such infections are to be developed. In this study we focus on genes we have found to be associated with patient outcome following bacteraemia caused by the major human pathogen Staphylococcus aureus . By examining the contribution these genes make to the ability of the bacteria to survive exposure to the antibacterial factors found in serum, we identify three novel serum resistance-associated genes, mdeA , mpsB and yycH . Detailed analysis of an MpsB mutant supports its previous association with the slow growing small colony variant (SCV) phenotype of S. aureus , and we demonstrate that the effect this mutation has on membrane potential prevents the activation of the Agr quorum sensing system, and as a consequence the mutant bacteria do not produce cytolytic toxins. Given the importance of both toxin production and immune evasion for the ability of S. aureus to cause disease, we believe that these findings explain the role of the mpsB gene as a mortality-associated locus during human disease.
    Type of Medium: Online Resource
    ISSN: 1350-0872 , 1465-2080
    URL: Article
    DOI: 10.1099/mic.0.001096
    Language: English
    Publisher: Microbiology Society
    Publication Date: 2021
    detail.hit.zdb_id: 2008736-6
    SSG: 12
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  • 3
    Online Resource
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    Image_3.TIF
    Frontiers Media SA ; 2019
    In:  Frontiers in Microbiology Vol. 10 ( 2019-5-10)
    Details
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 10 ( 2019-5-10)
    Type of Medium: Online Resource
    ISSN: 1664-302X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fmicb.2019.00863
    DOI: 10.3389/fmicb.2019.00863.s001
    DOI: 10.3389/fmicb.2019.00863.s002
    DOI: 10.3389/fmicb.2019.00863.s003
    DOI: 10.3389/fmicb.2019.00863.s004
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2587354-4
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  • 4
    Online Resource
    Online Resource
    Wall Teichoic Acids Facilitate the Release of Toxins from the Surface of Staphylococcus aureus
    American Society for Microbiology ; 2022
    In:  Microbiology Spectrum Vol. 10, No. 4 ( 2022-08-31)
    Details
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 10, No. 4 ( 2022-08-31)
    Abstract: A major feature of the pathogenicity of Staphylococcus aureus is its ability to secrete cytolytic toxins. This process involves the translocation of the toxins from the cytoplasm through the bacterial membrane and the cell wall to the external environment. The process of their movement through the membrane is relatively well defined, involving both general and toxin-specific secretory systems. Movement of the toxins through the cell wall was considered to involve the passive diffusion of the proteins through the porous cell wall structures; however, recent work suggests that this is more complex, and here we demonstrate a role for the wall teichoic acids (WTA) in this process. Utilizing a genome-wide association approach, we identified a polymorphism in the locus encoding the WTA biosynthetic machinery as associated with the cytolytic activity of the bacteria. We verified this association using an isogenic mutant set and found that WTA are required for the release of several cytolytic toxins from the bacterial cells. We show that this effect is mediated by a change in the electrostatic charge across the cell envelope that results from the loss of WTA. As a major target for the development of novel therapeutics, it is important that we fully understand the entire process of cytolytic toxin production and release. These findings open up a new aspect to the process of toxin release by a major human pathogen while also demonstrating that clinical isolates can utilize WTA production to vary their cytotoxicity, thereby altering their pathogenic capabilities. IMPORTANCE The production and release of cytolytic toxins is a critical aspect for the pathogenicity of many bacterial pathogens. In this study, we demonstrate a role for wall teichoic acids, molecules that are anchored to the peptidoglycan of the bacterial cell wall, in the release of toxins from S. aureus cells into the extracellular environment. Our findings suggest that this effect is mediated by a gradient of electrostatic charge which the presence of the negatively charged WTA molecules create across the cell envelope. This work brings an entirely new aspect to our understanding of the cytotoxicity of S. aureus and demonstrates a further means by which this major human pathogen can adapt its pathogenic capabilities.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    URL: Article
    DOI: 10.1128/spectrum.01011-22
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 2807133-5
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  • 5
    Online Resource
    Online Resource
    Little reason to call them small noncoding RNAs
    Frontiers Media SA ; 2023
    In:  Frontiers in Microbiology Vol. 14 ( 2023-6-29)
    Details
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 14 ( 2023-6-29)
    Abstract: Hundreds of different species of small RNAs can populate a bacterial cell. This small transcriptome contains important information for the adaptation of cellular physiology to environmental changes. Underlying cellular networks involving small RNAs are RNA–RNA and RNA-protein interactions, which are often intertwined. In addition, small RNAs can function as mRNAs. In general, small RNAs are referred to as noncoding because very few are known to contain translated open reading frames. In this article, we intend to highlight that the number of small RNAs that fall within the set of translated RNAs is bound to increase. In addition, we aim to emphasize that the dynamics of the small transcriptome involve different functional codes, not just the genetic code. Therefore, since the role of small RNAs is always code-driven, we believe that there is little reason to continue calling them small noncoding RNAs.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    URL: Article
    DOI: 10.3389/fmicb.2023.1191166
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2587354-4
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  • 6
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    Online Resource
    Editorial: Bacterial surface polymers
    Frontiers Media SA ; 2024
    In:  Frontiers in Cellular and Infection Microbiology Vol. 14 ( 2024-4-25)
    Details
    In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 14 ( 2024-4-25)
    Type of Medium: Online Resource
    ISSN: 2235-2988
    URL: Article
    DOI: 10.3389/fcimb.2024.1415799
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2619676-1
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  • 7
    Online Resource
    Online Resource
    Multilayer Regulation of Neisseria meningitidis NHBA at Physiologically Relevant Temperatures
    MDPI AG ; 2022
    In:  Microorganisms Vol. 10, No. 4 ( 2022-04-18), p. 834-
    Details
    In: Microorganisms, MDPI AG, Vol. 10, No. 4 ( 2022-04-18), p. 834-
    Abstract: Neisseria meningitidis colonizes the nasopharynx of humans, and pathogenic strains can disseminate into the bloodstream, causing septicemia and meningitis. NHBA is a surface-exposed lipoprotein expressed by all N. meningitidis strains in different isoforms. Diverse roles have been reported for NHBA in heparin-mediated serum resistance, biofilm formation, and adherence to host tissues. We determined that temperature controls the expression of NHBA in all strains tested, with increased levels at 30–32 °C compared to 37 °C. Higher NHBA expression at lower temperatures was measurable both at mRNA and protein levels, resulting in higher surface exposure. Detailed molecular analysis indicated that multiple molecular mechanisms are responsible for the thermoregulated NHBA expression. The comparison of mRNA steady-state levels and half-lives at 30 °C and 37 °C demonstrated an increased mRNA stability/translatability at lower temperatures. Protein stability was also impacted, resulting in higher NHBA stability at lower temperatures. Ultimately, increased NHBA expression resulted in higher susceptibility to complement-mediated killing. We propose that NHBA regulation in response to temperature downshift might be physiologically relevant during transmission and the initial step(s) of interaction within the host nasopharynx. Together these data describe the importance of NHBA both as a virulence factor and as a vaccine antigen during neisserial colonization and invasion.
    Type of Medium: Online Resource
    ISSN: 2076-2607
    URL: Article
    DOI: 10.3390/microorganisms10040834
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720891-6
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  • 8
    Online Resource
    Online Resource
    Multifaceted Interplay between Hfq and the Small RNA GssA in Pseudomonas aeruginosa
    American Society for Microbiology ; 2023
    In:  mBio Vol. 14, No. 1 ( 2023-02-28)
    Details
    In: mBio, American Society for Microbiology, Vol. 14, No. 1 ( 2023-02-28)
    Abstract: Behind the pathogenic lifestyle of Pseudomonas aeruginosa exists a complex regulatory network of intertwined switches at both the transcriptional and posttranscriptional levels. Major players that mediate translation regulation of several genes involved in host- P. aeruginosa interaction are small RNAs (sRNAs) and the Hfq protein. The canonical role of Hfq in sRNA-driven regulation is to act as a matchmaker between sRNAs and target mRNAs. Besides, the sRNA CrcZ is known to sequester Hfq and abrogate its function of translation repression of target mRNAs. In this study, we describe the novel sRNA GssA in the strain PA14 and its multifaceted interplay with Hfq. We show that GssA is multiresponsive to environmental and physiological signals and acts as an apical repressor of key bacterial functions in the human host such as the production of pyocyanin, utilization of glucose, and secretion of exotoxin A. We suggest that the main role of Hfq is not to directly assist GssA in its regulatory role but to repress GssA expression. In the case of pyocyanin production, we suggest that Hfq interplays with GssA also by converging a positive effect on this pathway. Furthermore, our results indicate that both Hfq and GssA play a positive role in anaerobic growth, possibly by regulating the respiratory chain. On the other hand, we show that GssA can modulate not only Hfq expression at both transcriptional and posttranscriptional levels but also that of CrcZ, thus potentially influencing the pleiotropic role of Hfq. IMPORTANCE The pathogenic lifestyle of the bacterium Pseudomonas aeruginosa , a leading cause of life-threatening infections in the airways of cystic fibrosis patients, is based on the fine regulation of virulence-associated factors. Regulatory small RNAs (sRNAs) and the RNA-binding protein Hfq are recognized key components within the P. aeruginosa regulatory networks involved in host-pathogen interaction. In this study, we characterized in the highly virulent P. aeruginosa strain PA14 the novel sRNA GssA. We found that it can establish a many-sided reciprocal interplay with Hfq which goes beyond the canonical mechanism of direct physical interaction that had previously been characterized for other sRNAs. Given that the Hfq-driven regulatory network of virulence factors is very broad and important for the progression of infection, we consider GssA as a new RNA target that can potentially be used to develop new antibacterial drugs.
    Type of Medium: Online Resource
    ISSN: 2150-7511
    URL: Article
    DOI: 10.1128/mbio.02418-22
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2023
    detail.hit.zdb_id: 2557172-2
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  • 9
    Online Resource
    Online Resource
    Table_3.XLSX
    Frontiers Media SA ; 2018
    In:  Frontiers in Microbiology Vol. 9 ( 2018-8-14)
    Details
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 9 ( 2018-8-14)
    Type of Medium: Online Resource
    ISSN: 1664-302X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fmicb.2018.01887
    DOI: 10.3389/fmicb.2018.01887.s001
    DOI: 10.3389/fmicb.2018.01887.s002
    DOI: 10.3389/fmicb.2018.01887.s003
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2018
    detail.hit.zdb_id: 2587354-4
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  • 10
    Online Resource
    Online Resource
    Targeted control of pneumolysin production by a mobile genetic element in Streptococcus pneumoniae
    Microbiology Society ; 2022
    In:  Microbial Genomics Vol. 8, No. 4 ( 2022-04-13)
    Details
    In: Microbial Genomics, Microbiology Society, Vol. 8, No. 4 ( 2022-04-13)
    Abstract: Streptococcus pneumoniae is a major human pathogen that can cause severe invasive diseases such as pneumonia, septicaemia and meningitis. Young children are at a particularly high risk, with an estimated 3–4 million cases of severe disease and between 300 000 and 500 000 deaths attributable to pneumococcal disease each year. The haemolytic toxin pneumolysin (Ply) is a primary virulence factor for this bacterium, yet despite its key role in pathogenesis, immune evasion and transmission, the regulation of Ply production is not well defined. Using a genome-wide association approach, we identified a large number of potential affectors of Ply activity, including a gene acquired horizontally on the antibiotic resistance-conferring Integrative and Conjugative Element (ICE) ICE Sp 23FST81. This gene encodes a novel modular protein, ZomB, which has an N-terminal UvrD-like helicase domain followed by two Cas4-like domains with potent ATP-dependent nuclease activity. We found the regulatory effect of ZomB to be specific for the ply operon, potentially mediated by its high affinity for the BOX repeats encoded therein. Using a murine model of pneumococcal colonization, we further demonstrate that a ZomB mutant strain colonizes both the upper respiratory tract and lungs at higher levels when compared to the wild-type strain. While the antibiotic resistance-conferring aspects of ICE Sp 23FST81 are often credited with contributing to the success of the S. pneumoniae lineages that acquire it, its ability to control the expression of a major virulence factor implicated in bacterial transmission is also likely to have played an important role.
    Type of Medium: Online Resource
    ISSN: 2057-5858
    URL: Article
    DOI: 10.1099/mgen.0.000784
    Language: English
    Publisher: Microbiology Society
    Publication Date: 2022
    detail.hit.zdb_id: 2835258-0
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