CpsY Influences Streptococcus iniae Cell Wall Adaptations Important for Neutrophil Intracellular Survival

Allen, Jonathan P.; Neely, Melody N.

doi:10.1128/iai.00027-12

Cited by 18 publications

(21 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CpsY regulates modifications of the bacterial cell wall in S. iniae that are necessary for resistance to neutrophil-mediated killing, as indicated by the increased sensitivity to lysozyme and altered expression of a peptidoglycan amidase (murA) in a CpsY-lacking strain of this species (29). Our RNA-seq analysis indicates that expression of the murA homolog of S. iniae in GAS (Spy0500 [murA2]) is also influenced by GAS CpsY.…”

Section: Spy0500])mentioning

confidence: 84%

“…The M5005_Spy0500 gene (here called murA2) encodes a putative N-acetylmuramoyl-L-alanine amidase that is 78% identical to the transcript identified by Allen and Neely as regulated by CpsY and annotated as murA in S. iniae (29). The gene annotated in M1T1 5448 as murA was not differentially expressed in the ()cpsY mutant.…”

Section: Discussionmentioning

confidence: 99%

“…CpsY shares homology (83% identity) with a LysR family transcriptional regulator of S. mutans (MetR), as well as to proteins in S. iniae (CpsY) and S. agalactiae (MtaR) that regulate methionine transport (25), amino acid metabolism (26), and resistance to neutrophilmediated killing and survival in vivo (27)(28)(29). This led us to hypothesize that CpsY functions as a transcriptional regulator of GAS metabolism required for survival in human host blood.…”

Section: Discussionmentioning

confidence: 99%

“…This analysis confirmed that CpsY activity is associated with low-level repression of mntE and Spy0500, as well as induction of emm1 and mur1.2. Further examination of the Spy0500 sequence found 79% identity to the N-acetylmuramoyl-L-alanine amidase encoded by the murA gene characterized as regulated by CpsY in S. iniae (29) and MtaR in S. agalactiae (26). Thus, it appears that the sequence annotated in the MGAS5005 genome as murA (M5005_Spy0548) does not correspond to the homolog of the CpsY-regulated murA characterized in other streptococci.…”

Section: Spy0500])mentioning

confidence: 99%

“…GAS CpsY displays 83% identity with MetR, a LysR family transcriptional regulator of Streptococcus mutans shown to activate transcription of genes involved in methionine biosynthesis (metE) and uptake (atmB) in a homocysteine-dependent manner (24). Homologs of CpsY found in Streptococcus iniae and Streptococcus agalactiae (MtaR) have been characterized as virulence determinants that regulate methionine transport (25), amino acid metabolism (26), and cell wall modifications necessary for resistance to neutrophilmediated killing and survival in vivo (27)(28)(29). Thus, CpsY appears to play a crucial role as a transcriptional regulator in the development of streptococcal invasive disease through the promotion of immune cell resistance and host niche adaptation.…”

mentioning

confidence: 99%

See 4 more Smart Citations

The Transcriptional Regulator CpsY Is Important for Innate Immune Evasion in Streptococcus pyogenes

et al. 2017

View full text Add to dashboard Cite

As an exclusively human pathogen, Streptococcus pyogenes (the group A streptococcus [GAS]) has specifically adapted to evade host innate immunity and survive in multiple tissue niches, including blood. GAS can overcome the metabolic constraints of the blood environment and expresses various immunomodulatory factors necessary for survival and immune cell resistance. Here we present our investigation of one such factor, the predicted LysR family transcriptional regulator CpsY. The encoding gene, cpsY, was initially identified as being required for GAS survival in a transposon-site hybridization (TraSH) screen in whole human blood. CpsY is homologous with transcriptional regulators of Streptococcus mutans (MetR), Streptococcus iniae (CpsY), and Streptococcus agalactiae (MtaR) that regulate methionine transport, amino acid metabolism, resistance to neutrophil-mediated killing, and survival in vivo. Our investigation indicated that CpsY is involved in GAS resistance to innate immune cells of its human host. However, GAS CpsY does not manifest the in vitro phenotypes of its homologs in other streptococcal species. GAS CpsY appears to regulate a small set of genes that is markedly different from the regulons of its homologs. The differential expression of these genes depends on the growth medium, and CpsY modestly influences their expression. The GAS CpsY regulon includes known virulence factors (mntE, speB, spd, nga [spn], prtS [SpyCEP], and sse) and cell surface-associated factors of GAS (emm1, mur1.2, sibA [cdhA], and M5005_Spy0500). Intriguingly, the loss of CpsY in GAS does not result in virulence defects in murine models of infection, suggesting that CpsY function in immune evasion is specific to the human host.

show abstract

Section: Spy0500])mentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Spy0500])mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

The Transcriptional Regulator CpsY Is Important for Innate Immune Evasion in Streptococcus pyogenes

et al. 2017

View full text Add to dashboard Cite

show abstract

Cationic antimicrobial peptide resistance mechanisms of streptococcal pathogens

LaRock

Nizet

2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

View full text Add to dashboard Cite

Cationic antimicrobial peptides (CAMPs) are critical front line contributors to host defense against invasive bacterial infection. These immune factors have direct killing activity toward microbes, but many pathogens are able to resist their effects. Group A Streptococcus, group B Streptococcus and Streptococcus pneumoniae are among the most common pathogens of humans and display a variety of phenotypic adaptations to resist CAMPs. Common themes of CAMP resistance mechanisms among the pathogenic streptococci are repulsion, sequestration, export, and destruction. Each pathogen has a different array of CAMP-resistant mechanisms, with invasive disease potential reflecting the utilization of several mechanisms that may act in synergy. Here we discuss recent progress in identifying the sources of CAMP resistance in the medically important Streptococcus genus. Further study of these mechanisms can contribute to our understanding of streptococcal pathogenesis, and may provide new therapeutic targets for therapy and disease prevention.

show abstract

Zebrafish as a model for zoonotic aquatic pathogens

Rowe¹,

Withey²,

Neely³

2014

Developmental & Comparative Immunology

Self Cite

View full text Add to dashboard Cite

Aquatic habitats harbor a multitude of bacterial species. Many of these bacteria can act as pathogens to aquatic species and/or non-aquatic organisms, including humans, that come into contact with contaminated water sources or colonized aquatic organisms. In many instances, the bacteria are not pathogenic to the aquatic species they colonize and are only considered pathogens when they come into contact with humans. There is a general lack of knowledge about how the environmental lifestyle of these pathogens allows them to persist, replicate and produce the necessary pathogenic mechanisms to successfully transmit to the human host and cause disease. Recently, the zebrafish infectious disease model has emerged as an ideal system for examining aquatic pathogens, both in the aquatic environment and during infection of the human host. This review will focus on how the zebrafish has been used successfully to analyze the pathogenesis of aquatic bacterial pathogens.

show abstract

CpsY Influences Streptococcus iniae Cell Wall Adaptations Important for Neutrophil Intracellular Survival

Cited by 18 publications

References 85 publications

The Transcriptional Regulator CpsY Is Important for Innate Immune Evasion in Streptococcus pyogenes

The Transcriptional Regulator CpsY Is Important for Innate Immune Evasion in Streptococcus pyogenes

Cationic antimicrobial peptide resistance mechanisms of streptococcal pathogens

Zebrafish as a model for zoonotic aquatic pathogens

Contact Info

Product

Resources

About