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Articles of Significant Interest in This Issue

DOI: 10.1128/IAI.00221-19
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A Transmembrane Protease Controls Staphylococcus aureus Quorum Sensing

Cyclic peptide signaling is critical for the pathogenesis of Staphylococcus aureus and other Gram-positive pathogens. Cosgriff et al. (e00019-19) identify a putative transmembrane protease that promotes the function of the S. aureus accessory gene regulator (Agr) peptide signaling system. This membrane regulator of Agr quorum sensing (MroQ) interfaces with Agr to increase virulence gene expression and promote pathogenesis. Experiments to probe where in the Agr system MroQ acts suggest that the peptide maturation module, but not the two-component system, depends on MroQ for optimal function. Together, these results expand the picture of cyclic peptide signaling in S. aureus.

New Regulator of Virulence Factor Production in Staphylococcus aureus

A key factor behind the success of Staphylococcus aureus as a pathogen is the arsenal of virulence factors it produces. The master regulator of their production is the Agr system, first discovered >30 years ago. Marroquin et al. (e00002-19) identify an uncharacterized membrane protease, MroQ, as a new regulator of Agr activity. They show that deletion of mroQ results in impaired virulence factor production, biofilm formation, pigmentation, and virulence in mice. These effects are mediated via the direct control of Agr activity by MroQ in a protease-dependent fashion, potentially functioning through interaction with the AgrC histidine kinase.

Patient Phenotypes Uncover Association between Coagulation and Acinetobacter baumannii Infection

Medical records combined with patient genetic information offer opportunities to uncover new associations between host factors and infectious disease. Choby et al. (e00031-19) identify increased risk for hospitalizations due to bacterial infections in patients with a polymorphism in the gene encoding coagulation factor X. Modeling factor X deficiency in mice demonstrated that factor X is pathological during systemic infection by Acinetobacter baumannii. During infection, mice experience an excessive immune response, which, in part, relies on factor X, and results in increased bacterial burdens and mortality. Together this work uses clinical outcomes to discover an association between factor X and bacterial infection.

A Novel Borrelia burgdorferi Gene Is Critical for Spirochete Population Expansion in the Skin

The leading vector-borne bacterial pathogen, Borrelia burgdorferi, enters the skin by the bite of an infected tick and spreads to various distal tissues leading to the debilitating symptoms of Lyme disease. The genetic factors important for B. burgdorferi dissemination remain largely unknown. Aranjuez et al. (e00887-18) identify a novel B. burgdorferi gene, bbk13, which contributes to disseminated infection by promoting spirochete proliferation in the skin. This work highlights the important influence of early expansion of B. burgdorferi in the skin on the outcome of infection and the potential for this event to serve as a novel therapeutic target for Lyme disease.

Gaining a Foothold in the Intestinal Tract

Enterococci are ubiquitous commensals and major causes of nosocomial infections. Gastrointestinal tract (GIT) colonization typically precedes enterococcal dissemination to otherwise sterile sites. However, the mechanisms underlying GIT colonization by enterococci are poorly characterized. Banla et al. (e00853-18) find that the enzymatic activity of sortase A promotes intestinal colonization. Furthermore, deletion of sortase-dependent proteins (SDPs; surface proteins that require the enzyme SrtA for proper localization) with mucin-binding activity impairs intestinal colonization. This result suggests that SDPs promote GIT colonization by mediating mucin binding. Mucin-SDP interactions therefore represent potential targets for therapies to disrupt GIT colonization by enterococci.

Host Response Does Not Wane during Toxoplasma Chronic Infection

The long-term consequences of Toxoplasma gondii chronic infection are poorly understood. To examine the host response throughout chronic infection, Garfoot et al. (e00024-19) analyze the transcriptional profile of mouse brains infected with T. gondii for 21 to 180 days. In both males and females, most genes that changed abundance due to infection were similar throughout infection, and many were related to immunological responses. Sex-specific differences were identified in two immune genes, although these differences did not result in obvious biological changes to the host response. This analysis highlights the robust, long-term host response to T. gondii and the similarities between sexes.

Strain-Specific Differences Influence Patient Mortality in Cryptococcal Meningitis

Cryptococcus neoformans is a common cause of cryptococcal meningitis in patients with advanced HIV, yet a clear role for pathogen genetic variation has remained elusive. By infecting mice with clinical strains of C. neoformans and comparing mouse and human survival, Mukaremera et al. (e00046-19) show a correlation between human and mouse mortality rates. Differences in virulence were strain specific, with similar mortality observed in humans and mice infected with the same strain, indicating that pathogen genetic variation influenced mortality. Additionally, these studies show that the mouse model is a robust tool to dissect C. neoformans genetic factors that influence human disease.

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Articles of Significant Interest in This Issue
Infection and Immunity Apr 2019, 87 (5) e00221-19; DOI: 10.1128/IAI.00221-19

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Articles of Significant Interest in This Issue
Infection and Immunity Apr 2019, 87 (5) e00221-19; DOI: 10.1128/IAI.00221-19
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  • Article
    • A Transmembrane Protease Controls Staphylococcus aureus Quorum Sensing
    • New Regulator of Virulence Factor Production in Staphylococcus aureus
    • Patient Phenotypes Uncover Association between Coagulation and Acinetobacter baumannii Infection
    • A Novel Borrelia burgdorferi Gene Is Critical for Spirochete Population Expansion in the Skin
    • Gaining a Foothold in the Intestinal Tract
    • Host Response Does Not Wane during Toxoplasma Chronic Infection
    • Strain-Specific Differences Influence Patient Mortality in Cryptococcal Meningitis
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