Lack of Association between theTlr4(Lpsd/Lpsd) Genotype and Increased Susceptibility to Escherichia coli Bladder Infections in Female C3H/HeJ Mice

Suhs, Kaleigh; Marthaler, Brodie; Welch, Rodney A.; Hopkins, Walter J.

doi:10.1128/mbio.00094-11

Cited by 16 publications

(10 citation statements)

References 17 publications

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“…Titers below the limit of detection were assigned a value of 1 for visualization on the log scale and 0 for statistical analyses. genetic locus (in comparison to C3H/HeN mice) that contributes to the well-known susceptibility of the C3H/HeJ strain to UTI (62), and thus, further studies were carried out to investigate the effect of GBS on TLR4-mediated processes.…”

Section: Resultsmentioning

confidence: 99%

Immune Modulation by Group B Streptococcus Influences Host Susceptibility to Urinary Tract Infection by Uropathogenic Escherichia coli

et al. 2012

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Urinary tract infection (UTI) is most often caused by uropathogenic Escherichia coli (UPEC). UPEC inoculation into the female urinary tract (UT) can occur through physical activities that expose the UT to an inherently polymicrobial periurethral, vaginal, or gastrointestinal flora. We report that a common urogenital inhabitant and opportunistic pathogen, group B Streptococcus (GBS), when present at the time of UPEC exposure, undergoes rapid UPEC-dependent exclusion from the murine urinary tract, yet it influences acute UPEC-host interactions and alters host susceptibility to persistent outcomes of bladder and kidney infection. GBS presence results in increased UPEC titers in the bladder lumen during acute infection and reduced inflammatory responses of murine macrophages to live UPEC or purified lipopolysaccharide (LPS), phenotypes that require GBS mimicry of host sialic acid residues. Taken together, these studies suggest that despite low titers, the presence of GBS at the time of polymicrobial UT exposure may be an overlooked risk factor for chronic pyelonephritis and recurrent UTI in susceptible groups, even if it is outcompeted and thus absent by the time of diagnosis.

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Section: Resultsmentioning

confidence: 99%

Immune Modulation by Group B Streptococcus Influences Host Susceptibility to Urinary Tract Infection by Uropathogenic Escherichia coli

et al. 2012

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“…2C). Due to defects in Toll-like receptor 4 (TLR4) and possibly other host factors, C3H/HeJ mice have attenuated inflammatory responses and are consequently hypersensitive to UTIs (31)(32)(33)(34)(35)(36). In total, these data indicate that cAMP-CRP is critical to the fitness of UPEC within the urinary tract of immunocompetent animals, probably due to regulatory effects of cAMP-CRP on factors that control bacterial resistance to stresses generated by stimulation of host inflammatory cascades.…”

Section: Resultsmentioning

confidence: 99%

Adenylate Cyclase and the Cyclic AMP Receptor Protein Modulate Stress Resistance and Virulence Capacity of Uropathogenic Escherichia coli

et al. 2013

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In many bacteria, the second messenger cyclic AMP (cAMP) interacts with the transcription factor cAMP receptor protein (CRP), forming active cAMP-CRP complexes that can control a multitude of cellular activities, including expanded carbon source utilization, stress response pathways, and virulence. Here, we assessed the role of cAMP-CRP as a regulator of stress resistance and virulence in uropathogenic Escherichia coli (UPEC), the principal cause of urinary tract infections worldwide. Deletion of genes encoding either CRP or CyaA, the enzyme responsible for cAMP synthesis, attenuates the ability of UPEC to colonize the bladder in a mouse infection model, dependent on intact innate host defenses. UPEC mutants lacking cAMP-CRP grow normally in the presence of glucose but are unable to utilize alternate carbon sources like amino acids, the primary nutrients available to UPEC within the urinary tract. Relative to the wild-type UPEC isolate, the cyaA and crp deletion mutants are sensitive to nitrosative stress and the superoxide generator methyl viologen but remarkably resistant to hydrogen peroxide (H 2 O 2 ) and acid stress. In the mutant strains, H 2 O 2 resistance correlates with elevated catalase activity attributable in part to enhanced translation of the alternate sigma factor RpoS. Acid resistance was promoted by both RpoS-independent and RpoS-dependent mechanisms, including expression of the RpoS-regulated DNA-binding ferritin-like protein Dps. We conclude that balanced input from many cAMP-CRP-responsive elements, including RpoS, is critical to the ability of UPEC to handle the nutrient limitations and severe environmental stresses present within the mammalian urinary tract. U nder homeostatic conditions, the mammalian urinary tract is maintained as a sterile environment through the production of antimicrobial peptides and other toxic compounds, the bulk flow of urine, innate immune cell surveillance mechanisms, and nutrient limitations (1-5). However, select microbial pathogens are capable of colonizing and infecting this normally inhospitable niche. Uropathogenic Escherichia coli (UPEC) is the major cause of urinary tract infections (UTI) worldwide, affecting millions and requiring billions of dollars for diagnosis and treatment annually (6). To overcome host defenses and effectively colonize the urinary tract, UPEC employs a variety of virulence factors and stress resistance mechanisms, including adhesive and motility organelles that mediate attachment to and invasion of host cells, toxins that disarm innate immune responses, and multiple iron-scavenging proteins (1, 7-9). The ability to sense and prioritize the use of limited carbon sources within the nutrient-poor environment of the urinary tract is also likely critical to the success of UPEC, but our understanding of the impact that bacterial metabolic pathways have on the establishment and progression of a UTI is incomplete.Within the urinary tract, UPEC relies largely on the catabolism of small peptides and amino acids for survival and growth (4). U...

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“…122,167,179 However, a recent study using Escherichia coli in a model of urinary tract infection suggest that the Tlr4 mutation is not the sole factor in the susceptibility of the C3H/HeJ mouse to infection, since C3H/HeOuJ female mice are also highly susceptible to bladder infection by E. coli. 150 Given these findings, additional factors (eg, from modifier genes) may prove to be relevant to the high susceptibility of these mice to gram-negative bacterial infections.…”

Section: Immune Variation Among Inbred Mouse Strains: Selected Examplesmentioning

confidence: 99%

“…130 However the C3H/HeJ-related strains-among them C3H/HeN and C3H/HeOuJ-have a functional TLR4 receptor and respond normally to LPS. 130,150 Increased susceptibility of C3H/HeJ mice to infections with several gram-negative bacteria has been attributed to the defect in the Tlr4 gene. 122,167,179 However, a recent study using Escherichia coli in a model of urinary tract infection suggest that the Tlr4 mutation is not the sole factor in the susceptibility of the C3H/HeJ mouse to infection, since C3H/HeOuJ female mice are also highly susceptible to bladder infection by E. coli.…”

Section: Immune Variation Among Inbred Mouse Strains: Selected Examplesmentioning

confidence: 99%

Immunological Variation Between Inbred Laboratory Mouse Strains

et al. 2011

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Inbred laboratory mouse strains are highly divergent in their immune response patterns as a result of genetic mutations and polymorphisms. The generation of genetically engineered mice (GEM) has, in the past, used embryonic stem (ES) cells for gene targeting from various 129 substrains followed by backcrossing into more fecund mouse strains. Although common inbred mice are considered ''immune competent,'' many have variations in their immune system-some of which have been described-that may affect the phenotype. Recognition of these immune variations among commonly used inbred mouse strains is essential for the accurate interpretation of expected phenotypes or those that may arise unexpectedly. In GEM developed to study specific components of the immune system, accurate evaluation of immune responses must take into consideration not only the gene of interest but also how the background strain and microbial milieu contribute to the manifestation of findings in these mice. This article discusses points to consider regarding immunological differences between the common inbred laboratory mouse strains, particularly in their use as background strains in GEM.

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Lack of Association between theTlr4(Lps^d/Lps^d) Genotype and Increased Susceptibility to Escherichia coli Bladder Infections in Female C3H/HeJ Mice

Cited by 16 publications

References 17 publications

Immune Modulation by Group B Streptococcus Influences Host Susceptibility to Urinary Tract Infection by Uropathogenic Escherichia coli

Immune Modulation by Group B Streptococcus Influences Host Susceptibility to Urinary Tract Infection by Uropathogenic Escherichia coli

Adenylate Cyclase and the Cyclic AMP Receptor Protein Modulate Stress Resistance and Virulence Capacity of Uropathogenic Escherichia coli

Immunological Variation Between Inbred Laboratory Mouse Strains

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