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 Long-Term Survival of Salmonella enterica Serovar Typhimurium Reveals an Infectious State That Is Underrepresented on Laboratory Media Containing Bile Salts

2009 ◽  
Vol 75 (14) ◽  
pp. 4923-4925 ◽  
Author(s):  
Dmitry Apel ◽  
Aaron P. White ◽  
Guntram A. Grassl ◽  
B. Brett Finlay ◽  
Michael G. Surette
Keyword(s):  
Salmonella Enterica ◽  
Bile Salts ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Term Survival ◽  
Long Term Survival ◽  
Selective Media ◽  
Serovar Typhimurium ◽  
Systemic Infections ◽  
Infectious State

ABSTRACT Cells in desiccated Salmonella enterica serovar Typhimurium rdar (red, dry, and rough) morphotype colonies were examined for culturability and infectivity after 30 months. Culturability decreased only 10-fold; however, cells were underrepresented on Salmonella selective media containing bile salts. These cells were mildly attenuated compared to the infectivity of freshly grown cells but still able to cause systemic infections in mice.

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 Survival and Filamentation of Salmonella entericaSerovar Enteritidis PT4 and Salmonella enterica Serovar Typhimurium DT104 at Low Water Activity

2000 ◽  
Vol 66 (4) ◽  
pp. 1274-1279 ◽  
Author(s):  
K. L. Mattick ◽  
F. Jørgensen ◽  
J. D. Legan ◽  
M. B. Cole ◽  
J. Porter ◽  
...  
Keyword(s):  
Water Activity ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Morphological Changes ◽  
Laboratory Data ◽  
Microbial Count ◽  
Worst Case ◽  
Term Survival ◽  
Serovar Typhimurium

ABSTRACT In this study we investigated the long-term survival of and morphological changes in Salmonella strains at low water activity (aw). Salmonella enterica serovar Enteritidis PT4 and Salmonella enterica serovar Typhimurium DT104 survived at low aw for long periods, but minimum humectant concentrations of 8% NaCl (aw, 0.95), 96% sucrose (aw, 0.94), and 32% glycerol (aw, 0.92) were bactericidal under most conditions. Salmonella rpoS mutants were usually more sensitive to bactericidal levels of NaCl, sucrose, and glycerol. At a lethal aw, incubation at 37°C resulted in more rapid loss of viability than incubation at 21°C. At aw values of 0.93 to 0.98, strains of S. enterica serovar Enteritidis and S. enterica serovar Typhimurium formed filaments, some of which were at least 200 μm long. Filamentation was independent of rpoS expression. When the preparations were returned to high-aw conditions, the filaments formed septa, and division was complete within approximately 2 to 3 h. The variable survival ofSalmonella strains at low aw highlights the importance of strain choice when researchers produce modelling data to simulate worst-case scenarios or conduct risk assessments based on laboratory data. The continued increase in Salmonellabiomass at low aw (without a concomitant increase in microbial count) would not have been detected by traditional microbiological enumeration tests if the tests had been performed immediately after low-aw storage. If Salmonellastrains form filaments in food products that have low awvalues (0.92 to 0.98), there are significant implications for public health and for designing methods for microbiological monitoring.

scholarly journals A network of Rab GTPases controls phagosome maturation and is modulated by Salmonella enterica serovar Typhimurium

2007 ◽  
Vol 176 (3) ◽  
pp. 263-268 ◽  
Author(s):  
Adam C. Smith ◽  
Won Do Heo ◽  
Virginie Braun ◽  
Xiuju Jiang ◽  
Chloe Macrae ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Dominant Negative ◽  
Rab Gtpases ◽  
Wild Type ◽  
Intracellular Growth ◽  
Non Invasive ◽  
Serovar Typhimurium ◽  
Guanosine Triphosphatase ◽  
Kinetics Of

Members of the Rab guanosine triphosphatase (GTPase) family are key regulators of membrane traffic. Here we examined the association of 48 Rabs with model phagosomes containing a non-invasive mutant of Salmonella enterica serovar Typhimurium (S. Typhimurium). This mutant traffics to lysosomes and allowed us to determine which Rabs localize to a maturing phagosome. In total, 18 Rabs associated with maturing phagosomes, each with its own kinetics of association. Dominant-negative mutants of Rab23 and 35 inhibited phagosome–lysosome fusion. A large number of Rab GTPases localized to wild-type Salmonella-containing vacuoles (SCVs), which do not fuse with lysosomes. However, some Rabs (8B, 13, 23, 32, and 35) were excluded from wild-type SCVs whereas others (5A, 5B, 5C, 7A, 11A, and 11B) were enriched on this compartment. Our studies demonstrate that a complex network of Rab GTPases controls endocytic progression to lysosomes and that this is modulated by S. Typhimurium to allow its intracellular growth.

scholarly journals Draft Genome Sequences of 19 Salmonella enterica Serovar Typhimurium [4,5:i:−] Strains Resistant to Nalidixic Acid from a Long-Term Outbreak in Italy: TABLE 1 

2015 ◽  
Vol 3 (4) ◽  
Author(s):  
Massimiliano Orsini ◽  
Iolanda Mangone ◽  
Adriano DiPasquale ◽  
Samuel Perticara ◽  
Lorena Sacchini ◽  
...  
Keyword(s):  
Nalidixic Acid ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Draft Genome ◽  
Central Italy ◽  
Genome Sequences ◽  
Serovar Typhimurium

Here, we present the draft genome sequences of 19 Salmonella enterica serovar Typhimurium monophasic variant [4,5:i:−] strains involved in a long-term salmonellosis outbreak that occurred in central Italy in 2013 to 2014.

scholarly journals Salmonella enterica Serovar Typhimurium Uses PbgA/YejM To Regulate Lipopolysaccharide Assembly during Bacteremia

2019 ◽  
Vol 88 (1) ◽  
Author(s):  
Melina B. Cian ◽  
Nicole P. Giordano ◽  
Revathi Masilamani ◽  
Keaton E. Minor ◽  
Zachary D. Dalebroux
Keyword(s):  
Salmonella Enterica ◽  
Lipid A ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Transmembrane Domain ◽  
Wild Type ◽  
Content Type ◽  
Serovar Typhimurium ◽  
Periplasmic Domain ◽  
Inner Membrane Protein ◽  
Substitution Mutations

ABSTRACT Salmonella enterica serovar Typhimurium (S. Typhimurium) relies upon the inner membrane protein PbgA to enhance outer membrane (OM) integrity and promote virulence in mice. The PbgA transmembrane domain (residues 1 to 190) is essential for viability, while the periplasmic domain (residues 191 to 586) is dispensable. Residues within the basic region (residues 191 to 245) bind acidic phosphates on polar phospholipids, like for cardiolipins, and are necessary for salmonella OM integrity. S. Typhimurium bacteria increase their OM cardiolipin concentrations during activation of the PhoPQ regulators. The mechanism involves PbgA’s periplasmic globular region (residues 245 to 586), but the biological role of increasing cardiolipins on the surface is not understood. Nonsynonymous polymorphisms in three essential lipopolysaccharide (LPS) synthesis regulators, lapB (also known as yciM), ftsH, and lpxC, variably suppressed the defects in OM integrity, rifampin resistance, survival in macrophages, and systemic colonization of mice in the pbgAΔ191–586 mutant (in which the PbgA periplasmic domain from residues 191 to 586 is deleted). Compared to the OMs of the wild-type salmonellae, the OMs of the pbgA mutants had increased levels of lipid A-core molecules, cardiolipins, and phosphatidylethanolamines and decreased levels of specific phospholipids with cyclopropanated fatty acids. Complementation and substitution mutations in LapB and LpxC generally restored the phospholipid and LPS assembly defects for the pbgA mutants. During bacteremia, mice infected with the pbgA mutants survived and cleared the bacteria, while animals infected with wild-type salmonellae succumbed within 1 week. Remarkably, wild-type mice survived asymptomatically with pbgA-lpxC salmonellae in their livers and spleens for months, but Toll-like receptor 4-deficient animals succumbed to these infections within roughly 1 week. In summary, S. Typhimurium uses PbgA to influence LPS assembly during stress in order to survive, adapt, and proliferate within the host environment.

scholarly journals A Plasmid-Encoded FetMP-Fls Iron Uptake System Confers Selective Advantages to Salmonella enterica Serovar Typhimurium in Growth under Iron-Restricted Conditions and for Infection of Mammalian Host Cells

2020 ◽  
Vol 8 (5) ◽  
pp. 630
Author(s):  
Vanesa García ◽  
Ana Herrero-Fresno ◽  
Rosaura Rodicio ◽  
Alfonso Felipe-López ◽  
Ignacio Montero ◽  
...  
Keyword(s):  
Iron Content ◽  
Salmonella Enterica ◽  
Iron Uptake ◽  
Type Strain ◽  
Wild Type Strain ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Iron Acquisition ◽  
Clinical Strain ◽  
Wild Type ◽  
Serovar Typhimurium

The resistance plasmid pUO-StVR2, derived from virulence plasmid pSLT, is widespread in clinical isolates of Salmonella enterica serovar Typhimurium recovered in Spain and other European countries. pUO-StVR2 carries several genes encoding a FetMP-Fls system, which could be involved in iron uptake. We therefore analyzed S. Typhimurium LSP 146/02, a clinical strain selected as representative of the isolates carrying the plasmid, and an otherwise isogenic mutant lacking four genes (fetMP-flsDA) of the fetMP-fls region. Growth curves and determination of the intracellular iron content under iron-restricted conditions demonstrated that deletion of these genes impairs iron acquisition. Thus, under these conditions, the mutant grew significantly worse than the wild-type strain, its iron content was significantly lower, and it was outcompeted by the wild-type strain in competition assays. Importantly, the strain lacking the fetMP-flsDA genes was less invasive in cultured epithelial HeLa cells and replicated poorly upon infection of RAW264.7 macrophages. The genes were introduced into S. Typhimurium ATCC 14028, which lacks the FetMP-Fls system, and this resulted in increased growth under iron limitation as well as an increased ability to multiply inside macrophages. These findings indicate that the FetMP-Fls iron acquisition system exceeds the benefits conferred by the other high-affinity iron uptake systems carried by ATCC 14028 and LSP 146/02. We proposed that effective iron acquisition by this system in conjunction with antimicrobial resistance encoded from the same plasmid have greatly contributed to the epidemic success of S. Typhimurium isolates harboring pUO-StVR2.

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 sciS, an icmF Homolog in Salmonella enterica Serovar Typhimurium, Limits Intracellular Replication and Decreases Virulence

2005 ◽  
Vol 73 (7) ◽  
pp. 4338-4345 ◽  
Author(s):  
Duncan A. Parsons ◽  
Fred Heffron
Keyword(s):  
Legionella Pneumophila ◽  
Salmonella Enterica ◽  
Wild Type Strain ◽  
Salmonella Enterica Serovar Typhimurium ◽  
The Body ◽  
Wild Type ◽  
Serovar Typhimurium ◽  
Intracellular Multiplication ◽  
Late Stages ◽  
Made In

ABSTRACT Salmonella enterica serovar Typhimurium utilizes macrophages to disseminate from the intestine to deeper tissues within the body. While S. enterica serovar Typhimurium has been shown to kill its host macrophage, it can persist intracellularly beyond 18 h postinfection. To identify factors involved in late stages of infection, we screened a transposon library made in S. enterica serovar Typhimurium for the ability to persist in J774 macrophages at 24 h postinfection. Through this screen, we identified a gene, sciS, found to be homologous to icmF in Legionella pneumophila. icmF, which is required for intracellular multiplication, is conserved in several gram-negative pathogens, and its homolog appears to have been acquired horizontally in S. enterica serovar Typhimurium. We found that an sciS mutant displayed increased intracellular numbers in J774 macrophages when compared to the wild-type strain at 24 h postinfection. sciS was maximally transcribed at 27 h postinfection and is repressed by SsrB, an activator of genes required for promoting intracellular survival. Finally, we demonstrate that an sciS mutant is hypervirulent in mice when administered intragastrically. Taken together, these data indicate a role for SciS in controlling intracellular bacterial levels at later stages of infection and attenuating virulence in a murine host

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