scholarly journals A PhoP-Regulated Outer Membrane Protease of Salmonella enterica Serovar Typhimurium Promotes Resistance to Alpha-Helical Antimicrobial Peptides

2000 ◽  
Vol 182 (14) ◽  
pp. 4077-4086 ◽  
Author(s):  
Tina Guina ◽  
Eugene C. Yi ◽  
Houle Wang ◽  
Murray Hackett ◽  
Samuel I. Miller
Keyword(s):  
Antimicrobial Peptides ◽  
Outer Membrane ◽  
Salmonella Enterica ◽  
Culture Medium ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Outer Membrane Proteins ◽  
Database Searching ◽  
Two Dimensional Gel Electrophoresis ◽  
Serovar Typhimurium ◽  
Dependent Mechanism

ABSTRACT The outer membrane protein contents of Salmonella enterica serovar Typhimurium strains with PhoP/PhoQ regulon mutations were compared by two-dimensional gel electrophoresis. At least 26 species of outer membrane proteins (OMPs) were identified as being regulated by PhoP/PhoQ activation. One PhoP/PhoQ-activated OMP was identified by semiautomated tandem mass spectrometry coupled with electronic database searching as PgtE, a member of theEscherichia coli OmpT and Yersinia pestis Pla family of outer membrane proteases. Salmonella PgtE expression promoted resistance to alpha-helical cationic antimicrobial peptides (α-CAMPs). Strains expressing PgtE cleaved C18G, an 18-residue α-CAMP present in culture medium, indicating that protease activity is likely to be the mechanism of OmpT-mediated resistance to α-CAMPs. PhoP/PhoQ did not regulate the transcription or export of PgtE, indicating that another PhoP/PhoQ-dependent mechanism is required for PgtE outer membrane localization. PgtE is a posttranscriptionally regulated component of the PhoP/PhoQ regulon that contributes toSalmonella resistance to innate immunity.

scholarly journals Correlation between Ceftriaxone Resistance of Salmonella enterica Serovar Typhimurium and Expression of Outer Membrane Proteins OmpW and Ail/OmpX-Like Protein, Which Are Regulated by BaeR of a Two-Component System

2005 ◽  
Vol 49 (9) ◽  
pp. 3955-3958 ◽  
Author(s):  
Wensi S. Hu ◽  
Pei-Chuan Li ◽  
Chao-Yin Cheng
Keyword(s):  
Membrane Proteins ◽  
Outer Membrane ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Outer Membrane Proteins ◽  
Regulator Gene ◽  
Two Component System ◽  
Component System ◽  
Two Component ◽  
Serovar Typhimurium

ABSTRACT Mutant 7F2 of Salmonella enterica serovar Typhimurium has a transposon inserted in the regulator gene baeR of a two-component system and showed a more-than-fourfold reduction in resistance to ceftriaxone. Complementation analysis suggested an association among the outer membrane proteins OmpW and STM3031, ceftriaxone resistance, and baeR.

scholarly journals Mechanism and Fitness Costs of PR-39 Resistance in Salmonella enterica Serovar Typhimurium LT2

2008 ◽  
Vol 52 (8) ◽  
pp. 2734-2741 ◽  
Author(s):  
Maria Pränting ◽  
Aurel Negrea ◽  
Mikael Rhen ◽  
Dan I. Andersson
Keyword(s):  
Antimicrobial Peptides ◽  
Salmonella Enterica ◽  
Culture Medium ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Wild Type ◽  
Term Survival ◽  
Resistance Development ◽  
Serovar Typhimurium ◽  
Reduced Rate

ABSTRACT PR-39 is a porcine antimicrobial peptide that kills bacteria with a mechanism that does not involve cell lysis. Here, we demonstrate that Salmonella enterica serovar Typhimurium can rapidly acquire mutations that reduce susceptibility to PR-39. Resistant mutants appeared at a rate of 0.4 × 10−6 per cell per generation. These mutants were about four times more resistant than the wild type and showed a greatly reduced rate of killing. Genetic analysis revealed mutations in the putative transport protein SbmA as being responsible for the observed resistance. These sbmA mutants were as fit as the wild-type parental strain as measured by growth rates in culture medium and mice and by long-term survival in stationary phase. These results suggest that resistance to certain antimicrobial peptides can rapidly develop without an obvious fitness cost for the bacteria and that resistance development could become a threat to the efficacy of antimicrobial peptides if used in a clinical setting.

scholarly journals The enzyme phosphoglucomutase (Pgm) is required by Salmonella enterica serovar Typhimurium for O-antigen production, resistance to antimicrobial peptides and in vivo fitness

Microbiology ◽  
2009 ◽  
Vol 155 (10) ◽  
pp. 3403-3410 ◽  
Author(s):  
G. K. Paterson ◽  
D. B. Cone ◽  
S. E. Peters ◽  
D. J. Maskell
Keyword(s):  
Antimicrobial Peptides ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Live Attenuated Vaccine ◽  
Antigen Production ◽  
O Antigen ◽  
Serovar Typhimurium

The enzyme phosphoglucomutase (Pgm) catalyses the interconversion of glucose 1-phosphate and glucose 6-phosphate and contributes to glycolysis and the generation of sugar nucleotides for biosynthesis. To assess the role of this enzyme in the biology of the pathogen Salmonella enterica serovar Typhimurium we have characterized a pgm deletion mutant in strain SL1344. Compared to SL1344, SL1344 pgm had impaired growth in vitro, was deficient in the ability to utilize galactose as a carbon source and displayed reduced O-antigen polymer length. The mutant was also more susceptible to antimicrobial peptides and showed decreased fitness in the mouse typhoid model. The in vivo phenotype of SL1344 pgm indicated a role for pgm in the early stages of infection, most likely through deficient O-antigen production. Although pgm mutants in other pathogens have potential as live attenuated vaccine strains, SL1344 pgm was not sufficiently attenuated for such use.

scholarly journals Azithromycin Inhibits the Formation of Flagellar Filaments without Suppressing Flagellin Synthesis in Salmonella enterica Serovar Typhimurium

2005 ◽  
Vol 49 (8) ◽  
pp. 3396-3403 ◽  
Author(s):  
Hidenori Matsui ◽  
Masahiro Eguchi ◽  
Katsufumi Ohsumi ◽  
Akio Nakamura ◽  
Yasunori Isshiki ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Culture Medium ◽  
Macrolide Antibiotic ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Bacterial Cells ◽  
Immunoblotting Analysis ◽  
Serovar Typhimurium ◽  
Methylase Gene ◽  
The One

ABSTRACT The present study shows that a sub-MIC of the macrolide antibiotic azithromycin (AZM) diminishes the virulence function of Salmonella enterica serovar Typhimurium. We first constructed an AZM-resistant strain (MS248) by introducing ermBC, an erythromycin ribosome methylase gene, into serovar Typhimurium. The MIC of AZM for MS248 exceeded 100 μg/ml. Second, we managed to determine the efficacy with which a sub-MIC of AZM reduced the virulence of MS248 in vitro. On the one hand, AZM (10 μg/ml) in the culture medium was unable to inhibit the total protein synthesis, growth rate, or survival within macrophages of MS248. On the other hand, AZM (10 μg/ml) reduced MS248's swarming and swimming motilities in addition to its invasive activity in Henle-407 cells. Electron micrographs revealed no flagellar filaments on the surface of MS248 after overnight growth in L broth supplemented with AZM (10 μg/ml). However, immunoblotting analysis showed that flagellin (FliC) was fully synthesized within the bacterial cells in the presence of AZM (10 μg/ml). In contrast, the same concentration of AZM reduced the export of FliC to the culture medium. These results indicate that a sub-MIC of AZM was able to affect the formation of flagellar filaments, specifically by reducing the amount of flagellin exported from bacterial cells, but it was not involved in suppressing the synthesis of flagellin. Unfortunately, AZM treatment was ineffective against murine salmonellosis caused by MS248.

scholarly journals Role of Receptor Proteins for Enterobactin and 2,3-Dihydroxybenzoylserine in Virulence of Salmonella enterica

2003 ◽  
Vol 71 (12) ◽  
pp. 6953-6961 ◽  
Author(s):  
W. Rabsch ◽  
U. Methner ◽  
W. Voigt ◽  
H. Tschäpe ◽  
R. Reissbrodt ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Parental Strain ◽  
Salmonella Enterica ◽  
Growth Promotion ◽  
Outer Membrane Proteins ◽  
Breakdown Product ◽  
Triple Mutant ◽  
Siderophore Receptors ◽  
Systemic Spread ◽  
Serovar Typhimurium

ABSTRACT Single, double, and triple mutants of an enterobactin-deficient mutant strain of Salmonella enterica serovar Typhimurium were constructed that were defective in the expression of the iron-regulated outer membrane proteins (IROMPs) FepA, IroN, and Cir, which are proposed to function as catecholate receptors. Uptake of naturally occurring and chemically synthesized catecholate molecules by these mutants was assessed in standard growth promotion assays. Unique patterns of uptake were identified for each IROMP; specifically, FepA and IroN were confirmed to be required for transport of enterobactin, and all three proteins were shown to function as receptors for the enterobactin breakdown product 2,3-dihydroxybenzoylserine. The fepA, iroN, and cir alleles were transduced to enterobactin-proficient strains of S. enterica serovar Typhimurium and S. enterica serovar Enteritidis, and the resulting phenotypes were confirmed by analysis of outer membrane protein profiles, by sensitivity to KP-736, a catecholate-cephalosporin conjugate, and by growth promotion tests on egg white agar. Intragastric infections of mice with the S. enterica serovar Typhimurium strains indicated that the parental strain and the fepA iroN double mutant were similarly virulent but that the fepA iroN cir triple mutant was significantly attenuated. Moreover, in mixed infections, the fepA iroN mutant showed similar cecal colonization and invasion of the liver to the parental strain, while the triple mutant showed significantly reduced cecal colonization and no measurable spread to the liver. Infections of 4-day-old chicks with S. enterica serovar Enteritidis strains also indicated that mutation of the fepA iroN genes did not significantly reduce cecal colonization and systemic spread compared with those of the parental strain. The results indicate that, while enterobactin uptake is not essential for the virulence of S. enterica serovars in mouse and chicken infection models, the ability to take up 2,3-dihydroxybenzoylserine via any of the three catecholate siderophore receptors appears to play an important role, since the S. enterica serovar Typhimurium triple mutant was significantly attenuated in the mouse model. Salmochelins appear not to be involved in the virulence of S. enterica.

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