Listeria monocytogenes is a model organism for cellular microbiology and host-pathogen interaction studies and an important food-borne pathogen widespread in the environment, thus representing an ...attractive model to study the evolution of virulence. The phylogenetic structure of L. monocytogenes was determined by sequencing internal portions of seven housekeeping genes (3,288 nucleotides) in 360 representative isolates. Fifty-eight of the 126 disclosed sequence types were grouped into seven well-demarcated clonal complexes (clones) that comprised almost 75% of clinical isolates. Each clone had a unique or dominant serotype (4b for clones 1, 2 and 4, 1/2b for clones 3 and 5, 1/2a for clone 7, and 1/2c for clone 9), with no association of clones with clinical forms of human listeriosis. Homologous recombination was extremely limited (r/m<1 for nucleotides), implying long-term genetic stability of multilocus genotypes over time. Bayesian analysis based on 438 SNPs recovered the three previously defined lineages, plus one unclassified isolate of mixed ancestry. The phylogenetic distribution of serotypes indicated that serotype 4b evolved once from 1/2b, the likely ancestral serotype of lineage I. Serotype 1/2c derived once from 1/2a, with reference strain EGDe (1/2a) likely representing an intermediate evolutionary state. In contrast to housekeeping genes, the virulence factor internalin (InlA) evolved by localized recombination resulting in a mosaic pattern, with convergent evolution indicative of natural selection towards a truncation of InlA protein. This work provides a reference evolutionary framework for future studies on L. monocytogenes epidemiology, ecology, and virulence.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The ability to cross host barriers is an essential virulence determinant of invasive microbial pathogens. Listeria monocytogenes is a model microorganism that crosses human intestinal and placental ...barriers, and causes severe maternofetal infections by an unknown mechanism. Several studies have helped to characterize the bacterial invasion proteins InlA and InlB. However, their respective species specificity has complicated investigations on their in vivo role. Here we describe two novel and complementary animal models for human listeriosis: the gerbil, a natural host for L. monocytogenes, and a knock-in mouse line ubiquitously expressing humanized E-cadherin. Using these two models, we uncover the essential and interdependent roles of InlA and InlB in fetoplacental listeriosis, and thereby decipher the molecular mechanism underlying the ability of a microbe to target and cross the placental barrier.
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Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Two species of Listeria are pathogenic; L. monocytogenes infects humans and animals, and L. ivanovii has been considered to infect ruminants only. We report L. ivanovii-associated gastroenteritis and ...bacteremia in a man. This isolate was indistinguishable from prototypic ruminant strains. L. ivanovii is thus an enteric opportunistic human pathogen.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
From 1999 through 2005, the incidence of listeriosis in France declined from 4.5 to 3.5 cases/million persons. In 2006, it increased to 4.7 cases/million persons. Extensive epidemiologic ...investigations of clusters in France have ruled out the occurrence of large foodborne disease outbreaks. In addition, no increase has occurred in pregnancy-associated cases or among persons <60 years of age who have no underlying disease. Increases have occurred mainly among persons >or=60 years of age and appear to be most pronounced for persons >or=70 years of age. In 8 other European countries, the incidence of listeriosis has increased, or remained relatively high, since 2000. As in France, these increases cannot be attributed to foodborne outbreaks, and no increase has been observed in pregnancy-associated cases. European countries appear to be experiencing an increased incidence of listeriosis among persons >or=60 years of age. The cause of this selective increased incidence is unknown.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Antimicrobial resistance is a major concern. Epidemiological studies have demonstrated direct relationships between antibiotic consumption and emergence/dissemination of resistant strains. Within the ...last decade, authors confounded spectrum activity and ecological effects and did not take into account several other factors playing important roles, such as impact on anaerobic flora, biliary elimination and sub-inhibitory concentration. The ecological impact of antibiotics on the gut microbiota by direct or indirect mechanisms reflects the breaking of the resistance barrier to colonization. To limit the impact of antibiotic therapy on gut microbiota, consideration of the spectrum of activity and route of elimination must be integrated into the decision. Various strategies to prevent (antimicrobial stewardship, action on residual antibiotics at colonic level) or cure dysbiosis (prebiotic, probiotic and fecal microbiota transplantation) have been introduced or are currently being developed.
Overconsumption of antibiotics in hospitals has led to policy implementation, including the control of antibiotic prescriptions. The impact of these policies on the evolution of antimicrobial ...resistance remains uncertain. In this work, we review the possible limits of such policies and focus on the need for a more efficient approach. Establishing a causal relationship between the introduction of new antibiotics and the emergence of new resistance mechanisms is difficult. Several studies have demonstrated that many resistance mechanisms existed before the discovery of antibiotics. Overconsumption of antibiotics has worsened the phenomenon of resistance. Antibiotics are responsible for intestinal dysbiosis, which is suspected of being the source of bacterial resistance. The complexity of the intestinal microbiota composition, the impact of the pharmacokinetic properties of antibiotics, and the multiplicity of other factors involved in the acquisition and emergence of multidrug-resistant organisms, lead us to think that de-escalation, in the absence of studies proving its effectiveness, is not the solution to limiting the spread of multidrug-resistant organisms. More studies are needed to clarify the ecological risk caused by different antibiotic classes. In the meantime, we need to concentrate our efforts on limiting antibiotic prescriptions to patients who really need it, and work on reducing the duration of these treatments.
To investigate the predictors and burden of hospital readmission with recurrent
Clostridioides difficile
infection (rCDI) in a large European healthcare system with a low prevalence of hyper-virulent
...C. difficile
clones. We conducted an inception cohort study based on an exhaustive health insurance database and including all survivors of a first hospital stay with CDI over a one-year period (2015) in France. Readmissions with rCDI were defined as a novel hospital stay with CDI within 12 weeks following discharge of the index hospitalization. Risk factors for readmission with rCDI were investigated through multivariate logistic regression analyses. Among the 14,739 survivors of the index hospital stay (females, 57.3%; median age, 74 58–84 years), 2135 (14.5%) required at least one readmission with rCDI. Independent predictors of readmission were age ≥ 65 years (adjusted odds ratio (aOR), 1.34, 95% confidence interval (CI), 1.21–1.49,
P
< 0.0001), immunosuppression (aOR, 1.27, 95% CI, 1.15–1.41,
P
< 0.0001), chronic renal failure (aOR, 1.29, 95% CI, 1.14–1.46,
P
< 0.0001), and a previous history of CDI (aOR, 2.05, 95% CI, 1.55–2.71,
P
< 0.0001). The cumulative number of risk factors was independently associated with the hazard of readmission. Mean acute care costs attributable to rCDI were 5619 ± 3594 Euros for readmissions with rCDI as primary diagnosis (mean length of stay, 11.3 ± 10.2 days) and 4851 ± 445 Euros for those with rCDI as secondary diagnosis (mean length of stay, 16.8 ± 18.2 days), for an estimated annual nation-wide cost of 14,946,632 Euros. Hospital readmissions with rCDI are common after an index episode and drive major healthcare expenditures with substantial bed occupancy, strengthening the need for efficient secondary prevention strategies in high-risk patients.
Clostridium difficile infection (CDI) is associated with a substantial Quality of life impact on patients that has not been so far measured with a generic validated instrument.
A prospective study ...was performed in 7 French acute-care settings in patients presenting with a bacteriologically-confirmed CDI. The EQ-5D-3 L was filled in by patients at 7 ± 2 days after CDI diagnosis to describe their state of health at that date as well as their state of health immediately before the CDI episode (baseline). Individual utility decrement was obtained by subtracting the corresponding utilities. The Quality Adjusted Life Year (QALY) loss was calculated by multiplying the days spent from baseline to the date of the interview, by the decrement of utility. A multivariate analysis of variance of the utility decrement according to CDI and patients characteristics was performed.
Eighty patients were enrolled (mean age: 69.4 years, 55% females). The utility scores dropped from a mean 0.542 (SD: 0.391) at baseline to 0.050 (SD: 0.404) during the CDI episode with a mean adjusted utility decrement of 0.492 (SD: 0.398) point. This decrement increased significantly with CDI severity (Zar score ≥ 3) (p = 0.001), in patients with a positive baseline utility (p = 0.032), in women as compared to men (p = 0.041) and in patients aged more than 65 years (p = 0.041). No association with the Charlson index was found. The associated QALY loss not integrating the excess mortality was 0.028 (SD: 0.053).
The impact on quality of life of CDI episodes is major and translates in a substantial QALY loss despite their short duration.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The major virulence factors of
(
) are enterotoxins A (TcdA) and B (TcdB). The study of toxins is a crucial step in exploring the virulence of this pathogen. Currently, the toxin purification process ...is either laborious and time-consuming in
or performed in heterologous hosts. Therefore, we propose a streamlined method to obtain functional toxins in
. Two
strains were generated, each harboring a sequence encoding a His-tag at the 3' end of
630∆
or
genes. Each toxin gene is expressed using the P
promoter, which is inducible by anhydro-tetracycline. The obtained purification yields were 0.28 mg and 0.1 mg per liter for rTcdA and rTcdB, respectively. In this study, we successfully developed a simple routine method that allows the production and purification of biologically active rTcdA and rTcdB toxins with similar activities compared to native toxins.
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