mig
 -
 14
 Is a
 Salmonella
 Gene That Plays a Role in Bacterial Resistance to Antimicrobial Peptides

Brodsky, Igor E.; Ernst, Robert K.; Miller, Samuel I.; Falkow, Stanley

doi:10.1128/jb.184.12.3203-3213.2002

Cited by 80 publications

(81 citation statements)

References 57 publications

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“…In the final step, the 4-amino-N-phenylbenzenesufonamide product was condensed with phenylisothiocyanate in dry tetrahydrofuran in the presence of triethylamine at reflux for 48 h. After concentration, the crude oily product was purified by flash chromatography on silica gel in acetone-hexane (1:3) to deliver LED209 as a white crystalline solid (melting point of 161 to 163°C) in 25% yield. The structure and purity of the product was unequivocally confirmed by 1 H NMR, which showed the expected resonances at ␦ 7.00 to 7.47 (9H, 5 ϫ m, ArH), 7.70 (5H, s, Ph), 10 MudJ mutagenesis. MudJ mutagenesis was done as described previously (35).…”

Section: Methodsmentioning

confidence: 85%

Genome-Wide Transposon Mutagenesis Identifies a Role for Host Neuroendocrine Stress Hormones in Regulating the Expression of Virulence Genes inSalmonella

et al. 2010

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Bacterial sensing of environmental signals plays a key role in regulating virulence and mediating bacteriumhost interactions. The sensing of the neuroendocrine stress hormones epinephrine (adrenaline) and norepinephrine (noradrenaline) plays an important role in modulating bacterial virulence. We used MudJ transposon mutagenesis to globally screen for genes regulated by neuroendocrine stress hormones in Salmonella enterica serovar Typhimurium. We identified eight hormone-regulated genes, including yhaK, iroC, nrdF, accC, yedP, STM3081, and the virulence-related genes virK and mig14. The mammalian ␣-adrenergic receptor antagonist phentolamine reversed the hormone-mediated effects on yhaK, virK, and mig14 but did not affect the other genes. The ␤-adrenergic receptor antagonist propranolol had no activity in these assays. The virK and mig14 genes are involved in antimicrobial peptide resistance, and phenotypic screens revealed that exposure to neuroendocrine hormones increased the sensitivity of S. Typhimurium to the antimicrobial peptide LL-37. A virK mutant and a virK mig14 double mutant also displayed increased sensitivity to LL-37. In contrast to enterohemorrhagic Escherichia coli (EHEC), we have found no role for the two-component systems QseBC and QseEF in the adrenergic regulation of any of the identified genes. Furthermore, hormone-regulated gene expression could not be blocked by the QseC inhibitor LED209, suggesting that sensing of hormones is mediated through alternative signaling pathways in S. Typhimurium. This study has identified a role for host-derived neuroendocrine stress hormones in downregulating S. Typhimurium virulence gene expression to the benefit of the host, thus providing further insights into the field of host-pathogen communication.

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Section: Methodsmentioning

confidence: 85%

Genome-Wide Transposon Mutagenesis Identifies a Role for Host Neuroendocrine Stress Hormones in Regulating the Expression of Virulence Genes inSalmonella

et al. 2010

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“…These modifications reduce the inflammatory properties of lipid A (LPS) and increase ST IN bacteria resistance to CAMPs and bile salts (8,16). ST IN bacteria also modify the proteins of the outer membrane through increased expression of Mig14, VirK, and PgtE that render ST IN bacteria more resistant to CAMPs (19,20). It is unclear what other advantages these modifications may have for bacterial survival and/or evasion.…”

mentioning

confidence: 99%

Salmonella typhimurium Coordinately Regulates FliC Location and Reduces Dendritic Cell Activation and Antigen Presentation to CD4+ T cells

Alaniz¹,

Cummings²,

Bergman

et al. 2006

The Journal of Immunology

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During infection, Salmonella transitions from an extracellular-phase (STEX, growth outside host cells) to an intracellular-phase (STIN, growth inside host cells): changes in gene expression mediate survival in the phagosome and modifies LPS and outer membrane protein expression, including altered production of FliC, an Ag recognized by immune CD4+ T cells. Previously, we demonstrated that systemic STIN bacteria repress FliC below the activation threshold of FliC-specific T cells. In this study, we tested the hypothesis that changes in FliC compartmentalization and bacterial responses triggered during the transition from STEX to STIN combine to reduce the ability of APCs to present FliC to CD4+ T cells. Approximately 50% of the Salmonella-specific CD4+ T cells from Salmonella-immune mice were FliC specific and produced IFN-γ, demonstrating the potent immunogenicity of FliC. FliC expressed by STEX bacteria was efficiently presented by splenic APCs to FliC-specific CD4+ T cells in vitro. However, STIN bacteria, except when lysed, expressed FliC within a protected intracellular compartment and evaded stimulation of FliC-specific T cells. The combination of STIN-mediated responses that reduced FliC bioavailability were overcome by dendritic cells (DCs), which presented intracellular FliC within heat-killed bacteria; however, this ability was abrogated by live bacterial infection. Furthermore, STIN bacteria, unlike STEX, limited DC activation as measured by increased MHC class II, CD86, TNF-α, and IL-12 expression. These data indicate that STIN bacteria restrict FliC bioavailability by Ag compartmentalization, and together with STIN bacterial responses, limit DC maturation and cytokine production. Together, these mechanisms may restrain DC-mediated activation of FliC-specific CD4+ T cells.

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“…This protein is required for full virulence and is under the control of the Salmonella PhoPPhoQ system (Valdivia et al, 2000). The mig-14 gene is strongly induced by polymyxin B in a phoP-independent manner and is necessary for resistance towards polymyxin B and other CAMPs (Brodsky et al, 2002(Brodsky et al, , 2005. The P. aeruginosa PA5003 is located in the core oligosaccharide biosynthesis gene cluster, downstream of PA5004 encoding a putative glycosyltransferase WapH (Lam et al, 2004;Matewish, 2004).…”

Section: Discussionmentioning

confidence: 99%

A Mig-14-like protein (PA5003) affects antimicrobial peptide recognition in Pseudomonas aeruginosa

et al. 2011

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The evolution of antibiotic resistance in pathogenic bacteria is a growing global health problem which is gradually making the treatment of infectious diseases less efficient. Antimicrobial peptides are small charged molecules found in organisms from the complete phylogenetic spectrum. The peptides are attractive candidates for novel drug development due to their activity against bacteria that are resistant to conventional antibiotics, and reports of peptide resistance are rare in the clinical setting. Paradoxically, many clinically relevant bacteria have mechanisms that can recognize and respond to the presence of cationic antimicrobial peptides (CAMPs) in the environment by changing the properties of the microbial surface thereby increasing the tolerance of the microbes towards the peptides. In Pseudomonas aeruginosa an essential component of this inducible tolerance mechanism is the lipopolysaccharide modification operon arnBCADTEF-PA3559 which encodes enzymes required for LPS alterations leading to increased antimicrobial peptide tolerance. The expression of the operon is induced by the presence of CAMPs in the environment but the molecular mechanisms underlying the cellular recognition of the peptides are poorly elucidated. In this work, we investigate the factors influencing arnB expression by transposon mutagenesis and arnB promoter green fluorescent protein reporters. We have identified a novel gene encoding a Mig-14-like protein that is required for recognition of the CAMPs colistin and Novispirin G10 by P. aeruginosa. Moreover, we show that this gene is also required for the formation of CAMP-tolerant subpopulations in P. aeruginosa hydrodynamic flow chamber biofilms. INTRODUCTIONAntimicrobial peptides are an integral part of the host defence against infection and have been found in most multi-cellular organisms (Zasloff, 2002). The peptides are small, often cationic and structurally diverse and display broad-spectrum antimicrobial activity against a range of bacteria (Brogden, 2005). Charge interaction between the cationic peptide and the anionic microbial membrane is thought to be a critical step in a process leading to microbial killing (Brogden, 2005). A number of other peptide activities have been identified, indicating roles as multifunctional mediators of immunity, inflammation and wound repair (Hiemstra et al., 2004). Cationic antimicrobial peptides (CAMPs) are evident alternatives for drug development due to their activity on bacteria resistant to conventional antibiotics (Hiemstra et al., 2004). The polymyxins such as colistin are cyclic CAMPs which are highly active against many Gram-negative bacteria and are extensively used in the treatment of Pseudomonas aeruginosa lung infections in patients with cystic fibrosis (Frederiksen et al., 1997;Hoeprich, 1970;Littlewood et al., 1985;Storm et al., 1977). The appearance of bacteria resistant to most classes of antibiotics and the shortage of novel antimicrobial agents with activity against Gramnegative micro-organisms have led to the reemergence ...

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mig - 14 Is a Salmonella Gene That Plays a Role in Bacterial Resistance to Antimicrobial Peptides

Cited by 80 publications

References 57 publications

Genome-Wide Transposon Mutagenesis Identifies a Role for Host Neuroendocrine Stress Hormones in Regulating the Expression of Virulence Genes inSalmonella

Genome-Wide Transposon Mutagenesis Identifies a Role for Host Neuroendocrine Stress Hormones in Regulating the Expression of Virulence Genes inSalmonella

Salmonella typhimurium Coordinately Regulates FliC Location and Reduces Dendritic Cell Activation and Antigen Presentation to CD4+ T cells

A Mig-14-like protein (PA5003) affects antimicrobial peptide recognition in Pseudomonas aeruginosa

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