scholarly journals Horizontally acquired regulatory gene activates ancestral regulatory system to promote Salmonella virulence

2020 ◽  
Vol 48 (19) ◽  
pp. 10832-10847
Author(s):  
Jeongjoon Choi ◽  
Eduardo A Groisman
Keyword(s):  
Salmonella Enterica Serovar Typhimurium ◽  
Regulatory Gene ◽  
Regulatory System ◽  
Bacterial Virulence ◽  
Ancestral Genome ◽  
Acidic Ph ◽  
Heat Stable ◽  
Serovar Typhimurium ◽  
Salmonella Virulence ◽  
Target Promoter

Abstract Horizontally acquired genes are typically regulated by ancestral regulators. This regulation enables expression of horizontally acquired genes to be coordinated with that of preexisting genes. Here, we report a singular example of the opposite regulation: a horizontally acquired gene that controls an ancestral regulator, thereby promoting bacterial virulence. We establish that the horizontally acquired regulatory gene ssrB is necessary to activate the ancestral regulatory system PhoP/PhoQ of Salmonella enterica serovar Typhimurium (S. Typhimurium) in mildly acidic pH, which S. Typhimurium experiences inside macrophages. SsrB promotes phoP transcription by binding upstream of the phoP promoter. SsrB also increases ugtL transcription by binding to the ugtL promoter region, where it overcomes gene silencing by the heat-stable nucleoid structuring protein H-NS, enhancing virulence. The largely non-pathogenic species S. bongori failed to activate PhoP/PhoQ in mildly acidic pH because it lacks both the ssrB gene and the SsrB binding site in the target promoter. Low Mg2+ activated PhoP/PhoQ in both S. bongori and ssrB-lacking S. Typhimurium, indicating that the SsrB requirement for PhoP/PhoQ activation is signal-dependent. By controlling the ancestral genome, horizontally acquired genes are responsible for more crucial abilities, including virulence, than currently thought.

Detection of Virulence Plasmid–Encoded Genes in Salmonella Typhimurium and Salmonella Kentucky Isolates Recovered from Commercially Processed Chicken Carcasses

2019 ◽  
Vol 82 (8) ◽  
pp. 1364-1368 ◽  
Author(s):  
RIZWANA TASMIN ◽  
PAUL A. GULIG ◽  
SALINA PARVEEN
Keyword(s):  
United States ◽  
Salmonella Typhimurium ◽  
Virulence Genes ◽  
Salmonella Enterica Serovar Typhimurium ◽  
The United States ◽  
Clinical Isolates ◽  
Virulence Plasmid ◽  
Chicken Carcass ◽  
Serovar Typhimurium ◽  
Salmonella Virulence

ABSTRACT Salmonella enterica serovar Typhimurium is one of the leading causes of nontyphoidal gastroenteritis of humans in the United States. Commercially processed poultry carcasses are frequently contaminated with Salmonella serovar Kentucky in the United States. The aim of the study was to detect the Salmonella virulence plasmid containing the spv genes from Salmonella isolates recovered from commercially processed chicken carcasses. A total of 144 Salmonella isolates (Salmonella Typhimurium, n = 72 and Salmonella Kentucky, n = 72) were used for isolation of plasmids and detection of corresponding virulence genes (spvA, spvB, and spvC). Only four (5.5%) Salmonella Typhimurium isolates tested positive for all three virulence genes and hence were classified as possessing the virulence plasmid. All isolates of Salmonella Kentucky were negative for the virulence plasmid and genes. These results indicate that the virulence plasmid, which is very common among clinical isolates of Typhimurium and other Salmonella serovars (e.g., Enteritidis, Dublin, Choleraesuis, Gallinarum, Pullorum, and Abortusovis), may not be present in a significant portion of commercially processed chicken carcass isolates.

scholarly journals Cystathionine β-Lyase Is Important for Virulence of Salmonella enterica Serovar Typhimurium

2004 ◽  
Vol 72 (6) ◽  
pp. 3310-3314 ◽  
Author(s):  
Linda J. Ejim ◽  
Vanessa M. D'Costa ◽  
Nadine H. Elowe ◽  
J. Concepción Loredo-Osti ◽  
Danielle Malo ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Biosynthetic Pathway ◽  
Antibacterial Agents ◽  
Antimicrobial Agents ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Systemic Infection ◽  
Bacterial Virulence ◽  
Methionine Biosynthesis ◽  
Insertional Inactivation ◽  
Serovar Typhimurium

ABSTRACT The biosynthesis of methionine in bacteria requires the mobilization of sulfur from Cys by the formation and degradation of cystathionine. Cystathionine β-lyase, encoded by metC in bacteria and STR3 in Schizosaccharomyces pombe, catalyzes the breakdown of cystathionine to homocysteine, the penultimate step in methionine biosynthesis. This enzyme has been suggested to be the target for pyridinamine antimicrobial agents. We have demonstrated, by using purified enzymes from bacteria and yeast, that cystathionine β-lyase is not the likely target of these agents. Nonetheless, an insertional inactivation of metC in Salmonella enterica serovar Typhimurium resulted in the attenuation of virulence in a mouse model of systemic infection. This result confirms a previous chemical validation of the Met biosynthetic pathway as a target for the development of antibacterial agents and demonstrates that cystathionine β-lyase is important for bacterial virulence.

scholarly journals Genetic Analysis of Colistin Resistance in Salmonella enterica Serovar Typhimurium

2009 ◽  
Vol 53 (6) ◽  
pp. 2298-2305 ◽  
Author(s):  
Song Sun ◽  
Aurel Negrea ◽  
Mikael Rhen ◽  
Dan I. Andersson
Keyword(s):  
Mutation Rate ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Regulatory System ◽  
Clinical Settings ◽  
Missense Mutations ◽  
Regulator Protein ◽  
Serovar Typhimurium ◽  
Sensor Kinases ◽  
Genes Encoding

ABSTRACT Colistin is a cyclic cationic peptide that kills gram-negative bacteria by interacting with and disrupting the outer membrane. We isolated 44 independent mutants in Salmonella enterica serovar Typhimurium with reduced susceptibility to colistin and identified 27 different missense mutations located in the pmrA and pmrB genes (encoding the regulator and sensor of a two-component regulatory system) that conferred increased resistance. By comparison of the two homologous sensor kinases, PmrB and EnvZ, the 22 missense mutations identified in pmrB were shown to be located in four different structural domains of the protein. All five pmrA mutations were located in the phosphate receiver domain of the regulator protein. The mutants appeared at a mutation rate of 0.6 × 10−6 per cell per generation. The MICs of colistin for the mutants increased 2- to 35-fold, and the extent of killing was reduced several orders of magnitude compared to the susceptible strain. The growth rates of the mutants were slightly reduced in both rich medium and M9-glycerol minimal medium, whereas growth in mice appeared unaffected by the pmrA and pmrB mutations. The low fitness costs and the high mutation rate suggest that mutants with reduced susceptibility to colistin could emerge in clinical settings.

scholarly journals YaeB, Expressed in Response to the Acidic pH in Macrophages, Promotes Intracellular Replication and Virulence of Salmonella Typhimurium

2019 ◽  
Vol 20 (18) ◽  
pp. 4339 ◽  
Author(s):  
Huan Zhang ◽  
Xiaorui Song ◽  
Peisheng Wang ◽  
Runxia Lv ◽  
Shuangshuang Ma ◽  
...  
Keyword(s):  
Salmonella Enterica Serovar Typhimurium ◽  
Intracellular Pathogen ◽  
Acidic Ph ◽  
Intracellular Replication ◽  
Global Regulator ◽  
Serovar Typhimurium ◽  
Survival And Growth ◽  
Bacterial Replication ◽  
Specific Transport System

Salmonella enterica serovar Typhimurium is a facultative intracellular pathogen that infects humans and animals. Survival and growth in host macrophages represents a crucial step for S. Typhimurium virulence. Many genes that are essential for S. Typhimurium proliferation in macrophages and associated with virulence are highly expressed during the intracellular lifecycle. yaeB, which encodes an RNA methyltransferase, is also upregulated during S. Typhimurium growth in macrophages. However, the involvement of YaeB in S. Typhimurium pathogenicity is still unclear. In this study, we investigated the role of YaeB in S. Typhimurium virulence. Deletion of yaeB significantly impaired S. Typhimurium growth in macrophages and virulence in mice. The effect of yaeB on pathogenicity was related to its activation of pstSCAB, a phosphate (Pi)-specific transport system that is verified here to be important for bacterial replication and virulence. Moreover, qRT-PCR data showed YaeB was induced by the acidic pH inside macrophages, and the acidic pH passed to YeaB through inhibiting global regulator histone-like nucleoid structuring (H-NS) which confirmed in this study can repress the expression of yaeB. Overall, these findings identified a new virulence regulatory network involving yaeB and provided valuable insights to the mechanisms through which acidic pH and low Pi regulate virulence.

scholarly journals CadC Has a Global Translational Effect during Acid Adaptation in Salmonella enterica Serovar Typhimurium

2007 ◽  
Vol 189 (6) ◽  
pp. 2417-2425 ◽  
Author(s):  
Yong Heon Lee ◽  
Bae Hoon Kim ◽  
Ji Hye Kim ◽  
Won Suck Yoon ◽  
Seong Ho Bang ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Regulatory System ◽  
Acid Tolerance ◽  
Negative Influence ◽  
Acid Adaptation ◽  
Proteomic Approach ◽  
Serovar Typhimurium ◽  
Tolerance Response ◽  
Porin Proteins

ABSTRACT In Salmonella enterica serovar Typhimurium, the membrane-localized CadC is a transcriptional activator of the cadBA operon, which contributes to the acid tolerance response. Unlike in Escherichia coli, in which transcription of cadC is constitutive, in S. enterica serovar Typhimurium cadC expression is induced by low pH and lysine. Inactivation of cadC suppresses the acid-sensitive phenotype of a cadA mutation, suggesting the existence of other CadC-dependent genes in addition to the cadBA operon. Using a proteomic approach, we identified 8 of the putative CadC-induced proteins and 15 of the putative CadC-repressed proteins. The former include porin proteins OmpC and OmpF. The latter include proteins involved in glycolysis, energy production, and stress tolerance. To better understand the altered levels of OmpC and OmpF, we compared expression of ompR in S. enterica serovar Typhimurium wild-type and cadC mutant strains and determined that CadC exerted a negative influence on ompR transcription. Taken together, our findings strongly suggest that CadC may be a global regulator involved in the OmpR regulatory system during acid adaptation.

scholarly journals Arginine-Dependent Acid Resistance in Salmonella enterica Serovar Typhimurium

2006 ◽  
Vol 188 (15) ◽  
pp. 5650-5653 ◽  
Author(s):  
Jasper Kieboom ◽  
Tjakko Abee
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Acid Resistance ◽  
Arginine Decarboxylase ◽  
Acidic Ph ◽  
E Coli ◽  
Serovar Typhimurium ◽  
Microaerobic Conditions ◽  
Acid Challenge

ABSTRACT Salmonella enterica serovar Typhimurium does not survive a pH 2.5 acid challenge under conditions similar to those used for Escherichia coli (J. W. Foster, Nat. Rev. Microbiol. 2:898-907, 2004). Here, we provide evidence that S. enterica serovar Typhimurium can display arginine-dependent acid resistance (AR) provided the cells are grown under anoxic conditions and not under the microaerobic conditions used for assessment of AR in E. coli. The role of the arginine decarboxylase pathway in Salmonella AR was shown by the loss of AR in mutants lacking adiA, which encodes arginine decarboxylase; adiC, which encodes the arginine-agmatine antiporter; or adiY, which encodes an AraC-like regulator. Transcription of adiA and adiC was found to be dependent on AdiY, anaerobiosis, and acidic pH.

Influence of RpoS, cAMP-receptor protein, and ppGpp on expression of the opgGH operon and osmoregulated periplasmic glucan content of Salmonella enterica serovar Typhimurium

2009 ◽  
Vol 55 (11) ◽  
pp. 1284-1293 ◽  
Author(s):  
Cristina S. Costa ◽  
Ramón A. Pizarro ◽  
Dora N. Antón
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Regulatory System ◽  
Receptor Protein ◽  
Transcriptional Level ◽  
Camp Receptor Protein ◽  
High Osmolarity ◽  
Serovar Typhimurium ◽  
Camp Receptor ◽  
Periplasmic Glucan

A transcriptional fusion (opgG1::MudJ) to the opgGH operon of Salmonella enterica serovar Typhimurium (S. Typhimurium) LT2, isolated by resistance to mecillinam, was used to study the influence of global regulators RpoS, ppGpp, and cAMP/cAMP-receptor protein (CRP) on expression of the opgGH operon and osmoregulated periplasmic glucan (OPG) content. Neither high growth medium osmolarity nor absence of ppGpp or CRP had important effects on opgG1::MudJ expression in exponential cultures. However, under the same conditions, OPG content was strongly decreased by high osmolarity or cAMP/CRP defectiveness, and reduced to a half by lack of ppGpp. In stationary cultures, high osmolarity as well as CRP loss caused significant descents in opgG1::MudJ expression that were compensated by inactivation of RpoS σ factor. No effect of RpoS inactivation on OPG content was observed. It is concluded that opgGH expression in S. Typhimurium is only slightly affected by high osmolarity, but is inversely modulated by RpoS level. On the other hand, osmolarity and the cAMP/CRP global regulatory system appear to control OPG content, either directly or indirectly, mainly at the post-transcriptional level.

scholarly journals Alteration of the Rugose Phenotype in waaG and ddhC Mutants of Salmonella enterica Serovar Typhimurium DT104 Is Associated with Inverse Production of Curli and Cellulose

2006 ◽  
Vol 72 (7) ◽  
pp. 5002-5012 ◽  
Author(s):  
Yuda Anriany ◽  
Surashri N. Sahu ◽  
Kimberly R. Wessels ◽  
Lindsay M. McCann ◽  
Sam W. Joseph
Keyword(s):  
Salmonella Enterica ◽  
Biofilm Formation ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Regulatory System ◽  
Cell Aggregation ◽  
Scanning Electron Micrographs ◽  
Serovar Typhimurium ◽  
Potential Component ◽  
Matrix Production ◽  
Opposing Effects

ABSTRACT The rugose (also known as wrinkled or rdar) phenotype in Salmonella enterica serovar Typhimurium DT104 Rv has been associated with cell aggregation and the ability, at low temperature under low-osmolarity conditions, to form pellicles and biofilms. Two Tn5 insertion mutations in genes that are involved in lipopolysaccharide (LPS) synthesis, ddhC (A1-8) and waaG (A1-9), of Rv resulted in diminished expression of colony rugosity. Scanning electron micrographs revealed that the ddhC mutant showed reduced amounts of extracellular matrix, while there was relatively more, profuse matrix production in the waaG mutant, compared to Rv. Both mutants appeared to produce decreased levels of curli, as judged by Western blot assays probed with anti-AgfA (curli) antibodies but, surprisingly, were observed to have increased amounts of cellulose relative to Rv. Comparison with a non-curli-producing mutant suggested that the alteration in curli production may have engendered the increased presence of cellulose. While both mutants had impaired biofilm formation when grown in rich medium with low osmolarity, they constitutively formed larger amounts of biofilms when the growth medium was supplemented with either glucose or a combination of glucose and NaCl. These observations indicated that LPS alterations may have opposing effects on biofilm formation in these mutants, depending upon either the presence or the absence of these osmolytes. The phenotypes of the waaG mutant were further confirmed in a constructed, nonpolar deletion mutant of S. enterica serovar Typhimurium LT2, where restoration to the wild-type phenotypes was accomplished by complementation. These results highlight the importance of an integral LPS, at both the O-antigen and core polysaccharide levels, in the modulation of curli protein and cellulose production, as well as in biofilm formation, thereby adding another potential component to the complex regulatory system which governs multicellular behaviors in S. enterica serovar Typhimurium.

scholarly journals Contribution of the PhoP/Q regulon to survival and replication of Salmonella enterica serovar Typhimurium in macrophages

Microbiology ◽  
2011 ◽  
Vol 157 (7) ◽  
pp. 2084-2093 ◽  
Author(s):  
Jessica A. Thompson ◽  
Mei Liu ◽  
Sophie Helaine ◽  
David W. Holden
Keyword(s):  
Mutant Strain ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Systemic Disease ◽  
Hydrolytic Enzymes ◽  
Regulatory System ◽  
Murine Macrophages ◽  
Mutant Strains ◽  
Serovar Typhimurium

The ability of serovars of Salmonella enterica to cause systemic disease is dependent upon their survival and replication within macrophages. To do this, bacteria must withstand or surmount bacteriostatic and bactericidal responses by the host cell, including the delivery of hydrolytic enzymes from lysosomes to the phagosome. The bacterial two-component regulatory system PhoP/Q has been implicated in avoidance of phagolysosomal fusion by S. enterica serovar Typhimurium (S. Typhimurium) in murine macrophages. In this study, the involvement of PhoP/Q-activated genes in avoidance of phagolysosomal fusion was analysed: of all the S. Typhimurium mutant strains tested, only an mgtC mutant strain partially reproduced the phenotype of the phoP mutant strain. As this gene is required for bacterial growth in magnesium-depleted conditions in vitro, the contributions of PhoP/Q to intramacrophage replication and survival were reappraised. Although PhoP/Q was required for both replication and survival of S. Typhimurium within murine macrophages, subsequent analysis of the kinetics of phagolysosomal fusion, taking account of differences in the replication rates of wild-type and phoP mutant strains, provided no evidence for a PhoP/Q-dependent role in this process. PhoP/Q appeared to act subsequent to the process of phagolysosomal avoidance and to promote replication of those bacteria that had already escaped a phagolysosomal fate. Therefore, we conclude that the PhoP/Q regulon enables S. Typhimurium to adapt to intramacrophage stresses other than phagolysosomal fusion.

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