Structural and electronic relaxations around substitutional Cr3+ and Fe3+ ions in corundum

International audienceThe local arrangement of atoms surrounding a substitutional Cr3+ and Fe3+ ion in α-Al2O3: Cr3+ (ruby) and in α-Al2O3:(Fe−Ti) (blue sapphire) has been studied experimentally using natural x-ray linear dichroism absorption at the Cr and Fe K edge. The isotropic and dichroic signals have been recorded using single crystals and a reliable method has been applied to remove diffraction peaks. Results given by the analysis of both signals are compared with ab initio density functional calculations. This study reveals that the introduction of an impurity ion in the structure leads to relaxations that are very local in nature. The oxygen atoms in the coordination shell relax to an arrangement similar to that for Cr in α-Cr2O3 or for Fe in α-Fe2O3. Aluminum or oxygen atoms at a farther distance are weakly affected by the presence of the impurity

Clostridium difficile ribotype 017–characterization, evolution and epidemiology of the dominant strain in Asia

Clostridium difficile ribotype (RT) 017 is an important toxigenic C. difficile RT which, due to a deletion in the repetitive region of the tcdA gene, only produces functional toxin B. Strains belonging to this RT were initially dismissed as nonpathogenic and circulated largely undetected for almost two decades until they rose to prominence following a series of outbreaks in the early 2000s. Despite lacking a functional toxin A, C. difficile RT 017 strains have been shown subsequently to be capable of causing disease as severe as that caused by strains producing both toxins A and B. While C. difficile RT 017 strains can be found in almost every continent today, epidemiological studies suggest that the RT is endemic in Asia and that the global spread of this MLST clade 4 lineage member is a relatively recent event. C. difficile RT 017 transmission appears to be mostly from human to human with only a handful of reports of isolations from animals. An important feature of C. difficile RT 017 strains is their resistance to several antimicrobials and this has been documented as a possible factor driving multiple outbreaks in different parts of the world. This review summarizes what is currently known regarding the emergence and evolution of strains belonging to C. difficile RT 017 as well as features that have allowed it to become an RT of global importance

Genomic and Phenotypic Analyses of Acinetobacter baumannii Isolates From Three Tertiary Care Hospitals in Thailand.

Antibiotic resistant strains of Acinetobacter baumannii are responsible for a large and increasing burden of nosocomial infections in Thailand and other countries of Southeast Asia. New approaches to their control and treatment are urgently needed and an attractive strategy is to remove the bacterial polysaccharide capsule, and thus the protection from the host's immune system. To examine phylogenetic relationships, distribution of capsule chemotypes, acquired antibiotic resistance determinants, susceptibility to complement and other traits associated with systemic infection, we sequenced 191 isolates from three tertiary referral hospitals in Thailand and used phenotypic assays to characterize key aspects of infectivity. Several distinct lineages were circulating in three hospitals and the majority belonged to global clonal group 2 (GC2). Very high levels of resistance to carbapenems and other front-line antibiotics were found, as were a number of widespread plasmid replicons. A high diversity of capsule genotypes was encountered, with only three of these (KL6, KL10, and KL47) showing more than 10% frequency. Almost 90% of GC2 isolates belonged to the most common capsule genotypes and were fully resistant to the bactericidal action of human serum complement, most likely protected by their polysaccharide capsule, which represents a key determinant of virulence for systemic infection. Our study further highlights the importance to develop therapeutic strategies to remove the polysaccharide capsule from extensively drug-resistant A. baumanii during the course of systemic infection

Sequential Vaccination With Heterologous Acinetobacter baumannii Strains Induces Broadly Reactive Antibody Responses

Antibody therapy may be an alternative treatment option for infections caused by the multi-drug resistant (MDR) bacterium Acinetobacter baumannii. As A. baumannii has multiple capsular serotypes, a universal antibody therapy would need to target conserved protein antigens rather than the capsular polysaccharides. We have immunized mice with single or multiple A. baumannii strains to induce antibody responses to protein antigens, and then assessed whether these responses provide cross-protection against a collection of genetically diverse clinical A. baumannii isolates. Immunized mice developed antibody responses to multiple protein antigens. Flow cytometry IgG binding assays and immunoblots demonstrated improved recognition of both homologous and heterologous clinical strains in sera from mice immunized with multiple strains compared to a single strain. The capsule partially inhibited bacterial recognition by IgG and the promotion of phagocytosis by human neutrophils. However, after immunization with multiple strains, serum antibodies to protein antigens promoted neutrophil phagocytosis of heterologous A. baumannii strains. In an infection model, mice immunized with multiple strains had lower bacterial counts in the spleen and liver following challenge with a heterologous strain. These data demonstrate that antibodies targeting protein antigens can improve immune recognition and protection against diverse A. baumannii strains, providing support for their use as an antibody therapy

Predictors of hospital mortality among septic ICU patients with Acinetobacter spp. bacteremia: A cohort study

BACKGROUND: We hypothesized that among septic ICU patients with Acinetobacter spp. bacteremia (Ac-BSI), carbapenem-resistant Acinetobacter spp. (CRAc) increase risk for inappropriate initial antibiotic therapy (non-IAAT), and non-IAAT is a predictor of hospital death. METHODS: We conducted a retrospective cohort study of adult septic ICU patients with Ac-BSI. Non-IAAT was defined as exposure to initially prescribed antibiotics not active against the pathogen based on in vitro susceptibility testing, and having no exposure to appropriate antimicrobial treatment within 24 hours of drawing positive culture. We compared patients who died to those who survived, and derived regression models to identify predictors of hospital mortality and of non-IAAT. RESULTS: Out of 131 patients with Ac-BSI, 65 (49.6%) died (non-survivors, NS). NS were older (63 [51, 76] vs. 56 [45, 66] years, p = 0.014), and sicker than survivors (S): APACHE II (24 [19, 31] vs. 18 [13, 22], p < 0.001) and Charlson (5 [2, 8] vs. 3 [1, 6], p = 0.009) scores. NS were also more likely than S to require pressors (75.4% vs. 42.4%, p < 0.001) and mechanical ventilation (75.4% vs. 53.0%, p = 0.008). Both CRAc (69.2% vs. 47.0%, p = 0.010) and non-IAAT (83.1% vs. 59.1%, p = 0.002) were more frequent among NS than S. In multivariate analyses, non-IAAT emerged as an independent predictor of hospital death (risk ratio [RR] 1.42, 95% confidence interval [CI] 1.10-1.58), while CRAc was the single strongest predictor of non-IAAT (RR 2.66, 95% CI 2.43-2.72). CONCLUSIONS: Among septic ICU patients with Ac-BSI, non-IAAT predicts mortality. Carbapenem resistance appears to mediate the relationship between non-IAAT and mortality

Anthrax Lethal Toxin Disrupts Intestinal Barrier Function and Causes Systemic Infections with Enteric Bacteria

A variety of intestinal pathogens have virulence factors that target mitogen activated protein kinase (MAPK) signaling pathways, including Bacillus anthracis. Anthrax lethal toxin (LT) has specific proteolytic activity against the upstream regulators of MAPKs, the MAPK kinases (MKKs). Using a murine model of intoxication, we show that LT causes the dose-dependent disruption of intestinal epithelial integrity, characterized by mucosal erosion, ulceration, and bleeding. This pathology correlates with an LT-dependent blockade of intestinal crypt cell proliferation, accompanied by marked apoptosis in the villus tips. C57BL/6J mice treated with intravenous LT nearly uniformly develop systemic infections with commensal enteric organisms within 72 hours of administration. LT-dependent intestinal pathology depends upon its proteolytic activity and is partially attenuated by co-administration of broad spectrum antibiotics, indicating that it is both a cause and an effect of infection. These findings indicate that targeting of MAPK signaling pathways by anthrax LT compromises the structural integrity of the mucosal layer, serving to undermine the effectiveness of the intestinal barrier. Combined with the well-described immunosuppressive effects of LT, this disruption of the intestinal barrier provides a potential mechanism for host invasion via the enteric route, a common portal of entry during the natural infection cycle of Bacillus anthracis

High Prevalence of Extended-Spectrum Beta Lactamases among Salmonella enterica Typhimurium Isolates from Pediatric Patients with Diarrhea in China

We investigated the extended-spectrum beta lactamases among 62 Salmonella enterica Typhimurium isolates recovered from children with diarrhea in a Chinese pediatric hospital. A large proportion of S. enterica Typhimurium isolates were resistant to multiple antimicrobial agents, including ampicillin (90.3%), tetracycline (80.6%), trimethoprim/sulfamethoxazole (74.2%), chloramphenicol (66.1%), cefotaxime (27.4%). Forty-nine (79.0%) of S. enterica Typhimurium isolates were positive for blaTEM-1b and resistant to ampicillin. Thirteen S. enterica Typhimurium isolates (21.0%) were positive for blaCTX-M-1-group and blaCTX-M-9-group, and all isolates harboring blaCTX-M genes were positive for ISEcp1. Two main clones (PFGE type A and D) accounted for nearly 70% of S. enterica Typhimurium isolates, and 7 CTX-M-producing isolates belonged to PFGE type D. Collectively, our data reveal multi-drug resistance and a high prevalence of extended spectrum beta lactamases among S. enterica Typhimurium isolates from children in China. In addition, we report the first identification of blaCTX-M-55 within Salmonella spp. Our data also suggest that clonal spread is responsible for the dissemination of S. enterica Typhimurium isolates

Prediction by Promoter Logic in Bacterial Quorum Sensing

Quorum-sensing systems mediate chemical communication between bacterial cells, coordinating cell-density-dependent processes like biofilm formation and virulence-factor expression. In the proteobacterial LuxI/LuxR quorum sensing paradigm, a signaling molecule generated by an enzyme (LuxI) diffuses between cells and allosterically stimulates a transcriptional regulator (LuxR) to activate its cognate promoter (pR). By expressing either LuxI or LuxR in positive feedback from pR, these versatile systems can generate smooth (monostable) or abrupt (bistable) density-dependent responses to suit the ecological context. Here we combine theory and experiment to demonstrate that the promoter logic of pR – its measured activity as a function of LuxI and LuxR levels – contains all the biochemical information required to quantitatively predict the responses of such feedback loops. The interplay of promoter logic with feedback topology underlies the versatility of the LuxI/LuxR paradigm: LuxR and LuxI positive-feedback systems show dramatically different responses, while a dual positive/negative-feedback system displays synchronized oscillations. These results highlight the dual utility of promoter logic: to probe microscopic parameters and predict macroscopic phenotype

The Sudden Dominance of blaCTX–M Harbouring Plasmids in Shigella spp. Circulating in Southern Vietnam

Shigellosis is a disease caused by bacteria belonging to Shigella spp. and is a leading cause of bacterial gastrointestinal infections in infants in unindustrialized countries. The Shigellae are dynamic and capable of rapid change when placed under selective pressure in a human population. Extended spectrum beta lactamases (ESBLs) are enzymes capable of degrading cephalosporins (a group of antimicrobial agents) and the genes that encode them are common in pathogenic E. coli and other related organisms in industrialized countries. In southern Vietnam, we have isolated multiple cephalosporin-resistant Shigella that express ESBLs. Furthermore, over two years these strains have replaced strains isolated from patients with shigellosis that cannot express ESBLs. Our work describes the genes responsible for this characteristic and we investigate one of the elements carrying one of these genes. These finding have implications for treatment of shigellosis and support the growing necessity for vaccine development. Our findings also may be pertinent for other countries undergoing a similar economic transition to Vietnam's and the corresponding effect on bacterial populations