ThesagA/pellocus does not regulate the expression of the M protein of the M1T1 lineage of group AStreptococcus

Zhou, Yang; Hanks, Tracey S.; Feng, Wenchao; Li, Jinquan; Liu, Guanghui; Mengyao, Liu; Lei, Benfang

doi:10.4161/viru.26413

Cited by 10 publications

(23 citation statements)

References 36 publications

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“…GAS strains MGAS2221 and 5448 are characterized isolates of invasive M1T1 GAS, which is associated with severe invasive infections (17,20). A derivative of MGAS2221 with the loss of M protein production (the MGAS2221 MϪ mutant) arising during laboratory passage has been described (28). These strains and their gene deletion mutants listed in Table 1 were statically grown at 37°C in 5% CO 2 in Todd-Hewitt broth supplemented with 0.2% yeast extract (THY).…”

Section: Methodsmentioning

confidence: 99%

“…The production of M protein by GAS was assessed by Western blotting as described previously (28). Quantitative real-time reverse transcription-PCR (RT-PCR) analyses were performed using the All-in-One first-strand cDNA synthesis kit and the All-in-One SYBR quantitative PCR (qPCR) mix from GeneCopoeia (Rockville, MD), as described previously (30).…”

Section: Methodsmentioning

confidence: 99%

“…This discrepancy raises the question as to whether Sda1 is really a critical factor for the emergence of SpeB AϪ variants of strain 5448 during infection. To address this question, we deleted the sda1 gene in 5448 using the procedure of passaging on THY agar plates for the second crossover as described by Zhou et al (28). As expected, a 5448 ⌬sda1 mutant had lost the majority of DNase activity in culture supernatant compared to that of the parent strain (Fig.…”

Section: Dnases Are Not Required For In Vivo Selection Of Spebmentioning

confidence: 99%

“…Diminished in vivo selection of SpeB A؊ variants of 5448 ⌬sda1 M؊ mutant. MGAS2221 can acquire secondary mutations that downregulate M protein production during the construction of gene deletion mutants or simple passage in THY (28). Therefore, we investigated whether M protein production-negative mutants could be obtained during construction of 5448 ⌬sda1 mutants and lose selection pressure for 5448 SpeB AϪ variants.…”

Section: Dnases Are Not Required For In Vivo Selection Of Spebmentioning

confidence: 99%

“…The emm gene encoding the M protein is required for the selection of 5448 SpeB AϪ variants (21), and gene deletion mutants of MGAS2221 may have a secondary spontaneous mutation that abolishes M protein production (28), which in turn abolishes the selection of SpeB AϪ variants. Thus, it was crucial to make sure that derivative strains of MGAS2221 had normal M protein production in tests for selection of SpeB AϪ variants.…”

Section: Dnases Are Not Required For In Vivo Selection Of Spebmentioning

confidence: 99%

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The Mga Regulon but Not Deoxyribonuclease Sda1 of Invasive M1T1 Group A Streptococcus Contributes to In Vivo Selection of CovRS Mutations and Resistance to Innate Immune Killing Mechanisms

Liu

Feng

et al. 2015

Infect Immun

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bInvasive M1T1 group A Streptococcus (GAS) can have a mutation in the regulatory system CovRS, and this mutation can render strains hypervirulent. Interestingly, via mechanisms that are not well understood, the host innate immune system's neutrophils select spontaneous M1T1 GAS CovRS hypervirulent mutants, thereby enhancing the pathogen's ability to evade immune killing. It has been reported that the DNase Sda1 is critical for the resistance of M1T1 strain 5448 to killing in human blood and provides pressure for in vivo selection of CovRS mutations. We reexamined the role of Sda1 in the selection of CovRS mutations and in GAS innate immune evasion. Deletion of sda1 or all DNase genes in M1T1 strain MGAS2221 did not alter emergence of CovRS mutants during murine infection. Deletion of sda1 in strain 5448 resulted in ⌬sda1 mutants with (5448 ⌬sda1 M؉ strain) and without (5448 ⌬sda1 M؊ strain) M protein production. The 5448 ⌬sda1 M؉ strain accumulated CovRS mutations in vivo and resisted killing in the bloodstream, whereas the 5448 ⌬sda1 M؊ strain lost in vivo selection of CovRS mutations and was sensitive to killing. The deletion of emm and a spontaneous Mga mutation in MGAS2221 reduced and prevented in vivo selection for CovRS mutants, respectively. Thus, in contrast to previous reports, Sda1 is not critical for in vivo selection of invasive M1T1 CovRS mutants and GAS resistance to innate immune killing mechanisms. In contrast, M protein and other Mga-regulated proteins contribute to the in vivo selection of M1T1 GAS CovRS mutants. These findings advance the understanding of the progression of invasive M1T1 GAS infections. The human pathogen group A Streptococcus (GAS) causes about 700 million cases of relatively mild, noninvasive pharyngitis and superficial skin infections annually. However, severe GAS infections, including severe invasive infections and acute rheumatic fever/rheumatic heart disease, can occur, causing approximately 517,000 deaths in the world each year (1). A globally disseminated M1T1 clone of serotype M1 GAS most frequently is associated with severe invasive infections in the United States (2-4). It is believed that the original M1T1 GAS clone evolved from the acquisitions of DNase Sda1-and superantigen SpeA-encoding prophages and an interserotype exchange of a 36-kb chromosomal region containing the toxin genes encoding NAD ϩ -glycohydrolase (NADase) and streptolysin O (SLO) with serotype M12 GAS (5-7). More recently, hypervirulent M1T1 GAS strains have been isolated, usually having mutations in the two-component regulatory system CovRS (also known as CsrRS) (8-12).CovRS is known to negatively regulate multiple virulence genes in GAS, including the capsule synthetase gene hasA, the interleukin-8 (IL-8)/CXC chemokine peptidase gene spyCEP, and the platelet-activating factor acetylhydrolase gene sse (13-18). Natural CovS mutations of invasive M1T1 isolates usually enhance the expression of these virulence genes and downregulate the production of the protease SpeB (SpeB AϪ , for the lack of the...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Dnases Are Not Required For In Vivo Selection Of Spebmentioning

confidence: 99%

Section: Dnases Are Not Required For In Vivo Selection Of Spebmentioning

confidence: 99%

Section: Dnases Are Not Required For In Vivo Selection Of Spebmentioning

confidence: 99%

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The Mga Regulon but Not Deoxyribonuclease Sda1 of Invasive M1T1 Group A Streptococcus Contributes to In Vivo Selection of CovRS Mutations and Resistance to Innate Immune Killing Mechanisms

Liu

Feng

et al. 2015

Infect Immun

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The emerging role of bacterial regulatory RNAs in disease

Eichner

Karlsson

Loh

2022

Trends in Microbiology

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The Regulatory Small RNA MarS Supports Virulence of Streptococcus pyogenes

Pappesch

Warnke

Mikkat³

et al. 2017

Sci Rep

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Small regulatory RNAs (sRNAs) play a role in the control of bacterial virulence gene expression. In this study, we investigated an sRNA that was identified in Streptococcus pyogenes (group A Streptococcus, GAS) but is conserved throughout various streptococci. In a deletion strain, expression of mga, the gene encoding the multiple virulence gene regulator, was reduced. Accordingly, transcript and proteome analyses revealed decreased expression of several Mga-activated genes. Therefore, and because the sRNA was shown to interact with the 5′ UTR of the mga transcript in a gel-shift assay, we designated it MarS for m ga-activating regulatory sRNA. Down-regulation of important virulence factors, including the antiphagocytic M-protein, led to increased susceptibility of the deletion strain to phagocytosis and reduced adherence to human keratinocytes. In a mouse infection model, the marS deletion mutant showed reduced dissemination to the liver, kidney, and spleen. Additionally, deletion of marS led to increased tolerance towards oxidative stress. Our in vitro and in vivo results indicate a modulating effect of MarS on virulence gene expression and on the pathogenic potential of GAS.

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ThesagA/pellocus does not regulate the expression of the M protein of the M1T1 lineage of group AStreptococcus

Abstract: (2013) The sagA/pel locus does not regulate the expression of the M protein of the M1T1 lineage of group A Streptococcus, Virulence, 4:8,[698][699][700][701][702][703][704][705][706]

Cited by 10 publications

References 36 publications

The Mga Regulon but Not Deoxyribonuclease Sda1 of Invasive M1T1 Group A Streptococcus Contributes to In Vivo Selection of CovRS Mutations and Resistance to Innate Immune Killing Mechanisms

The Mga Regulon but Not Deoxyribonuclease Sda1 of Invasive M1T1 Group A Streptococcus Contributes to In Vivo Selection of CovRS Mutations and Resistance to Innate Immune Killing Mechanisms

The emerging role of bacterial regulatory RNAs in disease

The Regulatory Small RNA MarS Supports Virulence of Streptococcus pyogenes

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