scholarly journals Effect of MarA-Like Proteins on Antibiotic Resistance and Virulence in Yersinia pestis

2009 ◽  
Vol 78 (1) ◽  
pp. 364-371 ◽  
Author(s):  
Ida M. Lister ◽  
Joan Mecsas ◽  
Stuart B. Levy
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Mouse Model ◽  
Yersinia Pestis ◽  
Antibiotic Susceptibility ◽  
Deletion Mutant ◽  
Transcriptional Regulator ◽  
Drug Susceptibility ◽  
Wild Type ◽  
Lung Colonization

ABSTRACT MarA, an AraC/XylS transcriptional regulator in Escherichia coli, affects drug susceptibility and virulence. Two MarA-like proteins have been found in Yersinia pestis: MarA47 and MarA48. Deletion or overexpression of these proteins in the attenuated KIM 1001 Δpgm strain led to a change in multidrug susceptibility (including susceptibility to clinically relevant drugs). Additionally, lung colonization by the marA47 or marA48 deletion mutant was decreased about 10-fold in a pneumonic plague mouse model. Complementation of the deletions by replacing the deleted genes on the chromosome restored wild-type characteristics. These findings show that two MarA homologs in Y. pestis affect antibiotic susceptibility and virulence.

scholarly journals The Periplasmic Protein MppA Requires an Additional Mutated Locus To Repress marA Expression in Escherichia coli

2003 ◽  
Vol 185 (4) ◽  
pp. 1465-1469 ◽  
Author(s):  
Xiaowen Bina ◽  
Vincent Perreten ◽  
Stuart B. Levy
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Antibiotic Susceptibility ◽  
Type Strain ◽  
Wild Type Strain ◽  
Binding Protein ◽  
Periplasmic Protein ◽  
Multiple Antibiotic Resistance ◽  
Wild Type ◽  
Expression In Escherichia Coli

ABSTRACT Escherichia coli strain TP985, which has an insertional mutation in the gene for the periplasmic murein tripeptide binding protein MppA, was previously reported to overproduce MarA and exhibit a multiple-antibiotic resistance (Mar) phenotype (H. Li and J. T. Park, J. Bacteriol. 181:4842-4847, 1999). We found that TP985 contained a previously unrecognized marR mutation which was responsible for the Mar phenotype. Transduction of the mppA mutation from TP985 to another wild-type strain did not affect antibiotic susceptibility. Overproduction of MppA repressed marA transcription in TP985 but not in other mppA or marR mutants. Therefore, TP985 contains an additional unknown mutation(s) that facilitates the repression of marA expression by MppA.

scholarly journals SdiA Aids Enterohemorrhagic Escherichia coli Carriage by Cattle Fed a Forage or Grain Diet

2013 ◽  
Vol 81 (9) ◽  
pp. 3472-3478 ◽  
Author(s):  
Haiqing Sheng ◽  
Y. N. Nguyen ◽  
Carolyn J. Hovde ◽  
Vanessa Sperandio
Keyword(s):  
Escherichia Coli ◽  
Type Strain ◽  
Deletion Mutant ◽  
Wild Type Strain ◽  
Rumen Fluid ◽  
Acid Resistance ◽  
Enterohemorrhagic Escherichia Coli ◽  
Dependent Manner ◽  
Bacterial Survival ◽  
Wild Type

ABSTRACTEnterohemorrhagicEscherichia coli(EHEC) causes hemorrhagic colitis and life-threatening complications. The main reservoirs for EHEC are healthy ruminants. We reported that SdiA senses acyl homoserine lactones (AHLs) in the bovine rumen to activate expression of the glutamate acid resistance (gad) genes priming EHEC's acid resistance before they pass into the acidic abomasum. Conversely, SdiA represses expression of the locus of enterocyte effacement (LEE) genes, whose expression is not required for bacterial survival in the rumen but is necessary for efficient colonization at the rectoanal junction (RAJ) mucosa. Our previous studies show that SdiA-dependent regulation was necessary for efficient EHEC colonization of cattle fed a grain diet. Here, we compared the SdiA role in EHEC colonization of cattle fed a forage hay diet. We detected AHLs in the rumen of cattle fed a hay diet, and these AHLs activatedgadgene expression in an SdiA-dependent manner. The rumen fluid and fecal samples from hay-fed cattle were near neutrality, while the same digesta samples from grain-fed animals were acidic. Cattle fed either grain or hay and challenged with EHEC orally carried the bacteria similarly. EHEC was cleared from the rumen within days and from the RAJ mucosa after approximately one month. In competition trials, where animals were challenged with both wild-type and SdiA deletion mutant bacteria, diet did not affect the outcome that the wild-type strain was better able to persist and colonize. However, the wild-type strain had a greater advantage over the SdiA deletion mutant at the RAJ mucosa among cattle fed the grain diet.

Antibiotic susceptibility profiles and frequency of resistance genes in clinical Shiga toxin-producing Escherichia coli isolates from Michigan over a 14-year period

2021 ◽  
Author(s):  
Sanjana Mukherjee ◽  
Heather M. Blankenship ◽  
Jose A. Rodrigues ◽  
Rebekah E. Mosci ◽  
James T. Rudrik ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Shiga Toxin ◽  
Antibiotic Susceptibility ◽  
Genetic Relatedness ◽  
Antibiotic Resistance Genes ◽  
Genomic Analysis ◽  
Mechanisms Of Resistance ◽  
Susceptibility Profiles

Background: Shiga toxin-producing Escherichia coli (STEC) is an important foodborne pathogen that contributes to over 250,000 infections in the US each year. Because antibiotics are not recommended for STEC infections, resistance in STEC has not been widely researched despite an increased likelihood for the transfer of resistance gene from STEC to opportunistic pathogens residing within the same microbial community. Methods: Between 2001 and 2014, 969 STEC isolates were collected from Michigan patients. Serotyping and antibiotic susceptibility profiles to clinically relevant antibiotics were determined using disc diffusion, while epidemiological data was used to identify factors associated with resistance. Whole genome sequencing was used to examine genetic relatedness and identify genetic determinants and mechanisms of resistance in the non-O157 isolates. Results: Increasing frequencies of resistance to at least one antibiotic was observed over the 14 years (p=0.01). While the non-O157 serogroups were more commonly resistant than O157 (Odds Ratio: 2.4; 95% Confidence Interval:1.43-4.05), the frequency of ampicillin resistance among O157 isolates was significantly higher in Michigan compared to the national average (p=0.03). Genomic analysis of 321 non-O157 isolates uncovered 32 distinct antibiotic resistance genes (ARGs). Although mutations in genes encoding resistance to ciprofloxacin and ampicillin were detected in four isolates, most of the horizontally acquired ARGs conferred resistance to aminoglycosides, β-lactams, sulfonamides and/or tetracycline. Conclusions: This study provides insight into the mechanisms of resistance in a large collection of clinical non-O157 STEC isolates and demonstrates that antibiotic resistance among all STEC serogroups has increased over time, prompting the need for enhanced surveillance.

scholarly journals Inhibition of the multiple antibiotic resistance (mar) operon in Escherichia coli by antisense DNA analogs.

1997 ◽  
Vol 41 (12) ◽  
pp. 2699-2704 ◽  
Author(s):  
D G White ◽  
K Maneewannakul ◽  
E von Hofe ◽  
M Zillman ◽  
W Eisenberg ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Antisense Oligonucleotides ◽  
Multiple Antibiotic Resistance ◽  
Wild Type ◽  
Lacz Expression ◽  
E Coli ◽  
Plasmid Construct ◽  
Dna Analogs ◽  
Susceptibility And Resistance

The multiple antibiotic resistance operon (marORAB) in Escherichia coli controls intrinsic susceptibility and resistance to multiple, structurally different antibiotics and other noxious agents. A plasmid construct with marA cloned in the antisense direction reduced LacZ expression from a constitutively expressed marA::lacZ translational fusion and inhibited the induced expression of LacZ in cells bearing the wild-type repressed fusion. The marA antisense construction also decreased the multiple antibiotic resistance of a Mar mutant. Two antisense phosphorothioate oligonucleotides, one targeted to marO and the other targeted to marA of the mar operon, introduced by heat shock or electroporation reduced LacZ expression in the strain having the marA::lacZ fusion. One antisense oligonucleotide, tested against a Mar mutant of E. coli ML308-225, increased the bactericidal activity of norfloxacin. These studies demonstrate the efficacy of exogenously delivered antisense oligonucleotides targeted to the marRAB operon in inhibiting expression of this chromosomal regulatory locus.

scholarly journals Natural Genetic Transformation of Clinical Isolates of Escherichia coli in Urine and Water

2002 ◽  
Vol 68 (1) ◽  
pp. 440-443 ◽  
Author(s):  
Markus Woegerbauer ◽  
Bernard Jenni ◽  
Florian Thalhammer ◽  
Wolfgang Graninger ◽  
Heinz Burgmann
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Current Knowledge ◽  
Antibiotic Resistance Genes ◽  
Aquatic Environments ◽  
Wild Type ◽  
E Coli ◽  
Naturally Occurring ◽  
Natural Genetic Transformation ◽  
Type Strains

ABSTRACT Transfer of plasmid-borne antibiotic resistance genes in Escherichia coli wild-type strains is possible by transformation under naturally occurring conditions in oligotrophic, aquatic environments containing physiologic concentrations of calcium. In contrast, transformation is suppressed in nitrogen-rich body fluids like urine, a common habitat of uropathogenic strains. Current knowledge indicates that transformation of these E. coli wild-type strains is of no relevance for the acquisition of resistance in this clinically important environment.

scholarly journals Loss of Regulatory Protein RfaH Attenuates Virulence of Uropathogenic Escherichia coli

2002 ◽  
Vol 70 (8) ◽  
pp. 4406-4413 ◽  
Author(s):  
Gábor Nagy ◽  
Ulrich Dobrindt ◽  
György Schneider ◽  
A. Salam Khan ◽  
Jörg Hacker ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Mouse Model ◽  
Type Strain ◽  
Wild Type Strain ◽  
Regulatory Protein ◽  
Wild Type ◽  
Serovar Typhimurium

ABSTRACT RfaH is a regulatory protein in Escherichia coli and Salmonella enterica serovar Typhimurium. Although it enhances expression of different factors that are proposed to play a role in bacterial virulence, a direct effect of RfaH on virulence has not been investigated so far. We report that inactivation of rfaH dramatically decreases the virulence of uropathogenic E. coli strain 536 in an ascending mouse model of urinary tract infection. The mortality rate caused by the wild-type strain in this assay is 100%, whereas that of its isogenic rfaH mutant does not exceed 18%. In the case of coinfection, the wild-type strain 536 shows higher potential to colonize the urinary tract even when it is outnumbered 100-fold by its rfaH mutant in the inoculum. In contrast to the wild-type strain, serum resistance of strain 536rfaH::cat is fully abolished. Furthermore, we give evidence that, besides a major decrease in the amount of hemin receptor ChuA (G. Nagy, U. Dobrindt, M. Kupfer, L. Emody, H. Karch, and J. Hacker, Infect. Immun. 69:1924-1928, 2001), loss of the RfaH protein results in an altered lipopolysaccharide phenotype as well as decreased expression of K15 capsule and alpha-hemolysin, whereas levels of other pathogenicity factors such as siderophores, flagella, Prf, and S fimbriae appear to be unaltered in strain 536rfaH::cat in comparison to the wild-type strain. trans complementation of the mutant strain with the rfaH gene restores wild-type levels of the affected virulence factors and consequently restitutes virulence in the mouse model of ascending urinary tract infection.

scholarly journals Deletion of Braun lipoprotein gene (lpp) and curing of plasmid pPCP1 dramatically alter the virulence of Yersinia pestis CO92 in a mouse model of pneumonic plague

Microbiology ◽  
2009 ◽  
Vol 155 (10) ◽  
pp. 3247-3259 ◽  
Author(s):  
Stacy L. Agar ◽  
Jian Sha ◽  
Wallace B. Baze ◽  
Tatiana E. Erova ◽  
Sheri M. Foltz ◽  
...  
Keyword(s):  
Mouse Model ◽  
Yersinia Pestis ◽  
Mutant Strain ◽  
Tissue Injury ◽  
Virulence Plasmid ◽  
Wild Type ◽  
Pneumonic Plague ◽  
Cytokines And Chemokines ◽  
Tissue Homogenates

Deletion of the murein (Braun) lipoprotein gene, lpp, attenuates the Yersinia pestis CO92 strain in mouse models of bubonic and pneumonic plague. In this report, we characterized the virulence of strains from which the plasminogen activating protease (pla)-encoding pPCP1 plasmid was cured from either the wild-type (WT) or the Δlpp mutant strain of Y. pestis CO92 in the mouse model of pneumonic infection. We noted a significantly increased survival rate in mice infected with the Y. pestis pPCP−/Δlpp mutant strain up to a dose of 5000 LD50. Additionally, mice challenged with the pPCP − /Δlpp strain had substantially less tissue injury and a strong decrease in the levels of most cytokines and chemokines in tissue homogenates and sera when compared with the WT-infected group. Importantly, the Y. pestis pPCP − /Δlpp mutant strain was detectable in high numbers in the livers and spleens of some of the infected mice. In the lungs of pPCP − /Δlpp mutant-challenged animals, however, bacterial numbers dropped at 48 h after infection when compared with tissue homogenates from 1 h post-infection. Similarly, we noted that this mutant was unable to survive within murine macrophages in an in vitro assay, whereas survivability of the pPCP− mutant within the macrophage environment was similar to that of the WT. Taken together, our data indicated that a significant and possibly synergistic attenuation in bacterial virulence occurred in a mouse model of pneumonic plague when both the lpp gene and the virulence plasmid pPCP1 encoding the pla gene were deleted from Y. pestis.

scholarly journals Pathogenicity of Yersinia pestis Synthesis of 1-Dephosphorylated Lipid A

2013 ◽  
Vol 81 (4) ◽  
pp. 1172-1185 ◽  
Author(s):  
Wei Sun ◽  
David A. Six ◽  
C. Michael Reynolds ◽  
Hak Suk Chung ◽  
Christian R. H. Raetz ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Escherichia Coli ◽  
Yersinia Pestis ◽  
Francisella Tularensis ◽  
Inflammatory Reaction ◽  
Lipid A ◽  
Lethal Dose ◽  
Wild Type ◽  
Content Type ◽  
Significant Attenuation

ABSTRACTSynthesis ofEscherichia coliLpxL, which transfers a secondary laurate chain to the 2′ position of lipid A, inYersinia pestisproduced bisphosphoryl hexa-acylated lipid A at 37°C, leading to significant attenuation of virulence. Our previous observations also indicated that strain χ10015(pCD1Ap) (ΔlpxP32::PlpxLlpxL) stimulated a strong inflammatory reaction but sickened mice before recovery and retained virulence via intranasal (i.n.) infection. The development of live, attenuatedY. pestisvaccines may be facilitated by detoxification of its lipopolysaccharide (LPS). Heterologous expression of the lipid A 1-phosphatase, LpxE, fromFrancisella tularensisinY. pestisyields predominantly 1-dephosphorylated lipid A, as confirmed by mass spectrometry. Results indicated that expression of LpxE on top of LpxL provided no significant reduction in virulence ofY. pestisin mice when it was administered i.n. but actually reduced the 50% lethal dose (LD50) by 3 orders of magnitude when the strain was administered subcutaneously (s.c.). Additionally, LpxE synthesis in wild-typeY. pestisKIM6+(pCD1Ap) led to slight attenuation by s.c. inoculation but no virulence change by i.n. inoculation in mice. In contrast toSalmonella enterica, expression of LpxE does not attenuate the virulence ofY. pestis.

scholarly journals Yersinia pestisacrAB-tolCin Antibiotic Resistance and Virulence

2011 ◽  
Vol 56 (2) ◽  
pp. 1120-1123 ◽  
Author(s):  
Ida M. Lister ◽  
Connor Raftery ◽  
Joan Mecsas ◽  
Stuart B. Levy
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Yersinia Pestis ◽  
Pathogenic Bacteria ◽  
Efflux Pump ◽  
Efflux Pump Inhibitor ◽  
Content Type ◽  
Increased Susceptibility

ABSTRACTThe efflux pump AcrAB is important in the antibiotic resistance and virulence of several pathogenic bacteria. We report that deletion of theYersinia pestisAcrAB-TolC homolog leads to increased susceptibility to diverse substrates, including, though unlike inEscherichia coli, the aminoglycosides. Neither is theY. pestispump affected by the efflux pump inhibitor phenylalanine-arginine beta-naphthylamide. In mouse plague models, pump deletion does not have a significant effect on tissue colonization.

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