Abstract Gram-positive organisms are responsible for some of the most serious of human infections. Resistance to front-line antimicrobial agents can complicate otherwise curative therapy. These ...organisms possess multiple drug resistance mechanisms, with drug efflux being a significant contributing factor. Efflux proteins belonging to all five transporter families are involved, and frequently can transport multiple structurally unrelated compounds resulting in a multidrug resistance (MDR) phenotype. In addition to clinically relevant antimicrobial agents, MDR efflux proteins can transport environmental biocides and disinfectants which may allow persistence in the healthcare environment and subsequent acquisition by patients or staff. Intensive research on MDR efflux proteins and the regulation of expression of their genes is ongoing, providing some insight into the mechanisms of multidrug recognition and transport. Inhibitors of many of these proteins have been identified, including drugs currently being used for other indications. Structural modifications guided by structure-activity studies have resulted in the identification of potent compounds. However, lack of broad-spectrum pump inhibition combined with potential toxicity has hampered progress. Further work is required to gain a detailed understanding of the multidrug recognition process, followed by application of this knowledge in the design of safer and more highly potent inhibitors.
The atmospheric concentration of methane (CH
4), a major greenhouse gas, is mainly controlled by the activities of methane-producing (methanogens) and methane-consuming (methanotrophs) ...microorganisms. Freshwater lakes are identified as one of the main CH
4 sources, as it was estimated that they contribute to 6–16% of natural CH
4 emissions. It is therefore critical to better understanding the biogeochemical cycling of CH
4 in these ecosystems. In this paper, the effects of environmental factors on methanogenic and methanotrophic rates are reviewed and an inventory of the methanogens and methanotrophs at the genus/species level in freshwater lakes is given. We focus on the anaerobic oxidation of methane, which is a still poorly known process but increasingly reported in freshwater lakes.
The self-binding of bacterial cells, or autoaggregation, is, together with surface colonization, one of the first steps in the formation of a mature biofilm. In this work, the autoaggregation of B. ...subtilis in dilute bacterial suspensions was studied. The dynamics of cell lysis, eDNA release, and bacterial autoaggregate assembly were determined and related to the spatial autocorrelation of bacterial cells in dilute planktonic bacterial suspensions. The non-random distribution of cells was associated with an eDNA network, which stabilized the initial bacterial cell-cell aggregates. Upon the addition of DNase I, the aggregates were dispersed. The release of eDNA during cell lysis allows for the entrapment of bacterial drifters at a radius several times the size of the dying bacteria. The size of bacterial aggregates increased from 2 to about 100 μm in diameter in dilute bacterial suspensions. The results suggest that B. subtilis cells form previously unnoticed continuum of autoaggregate structures during planktonic growth.
A joint effect of bacteria and genetics Nusinovich, Yevgeniya
Science (American Association for the Advancement of Science),
2016-Dec-16, 2016-12-16, 20161216, Letnik:
354, Številka:
6318
Journal Article
Innovative approaches to the use of existing antibiotics is an important strategy in efforts to address the escalating antimicrobial resistance crisis. We report a new approach to the treatment of ...methicillin-resistant Staphylococcus aureus (MRSA) infections by demonstrating that oxacillin can be used to significantly attenuate the virulence of MRSA despite the pathogen being resistant to this drug. Using mechanistic in vitro assays and in vivo models of invasive pneumonia and sepsis, we show that oxacillin-treated MRSA strains are significantly attenuated in virulence. This effect is based primarily on the oxacillin-dependent repression of the accessory gene regulator quorum-sensing system and altered cell wall architecture, which in turn lead to increased susceptibility to host killing of MRSA. Our data indicate that ß-lactam antibiotics should be included in the treatment regimen as an adjunct antivirulence therapy for patients with MRSA infections. This would represent an important change to current clinical practice for treatment of MRSA infection, with the potential to significantly improve patient outcomes in a safe, cost-effective manner.
Lake bacteria make methane from P Wigginton, Nicholas S.
Science (American Association for the Advancement of Science),
11/2016, Letnik:
354, Številka:
6313
Journal Article
We investigated the effects of free ammonia (FA) and free nitrous acid (FNA) concentrations on the predominant ammonia-oxidizing bacteria (AOB) and the emission of nitrous oxide (N sub(2)O) in a ...lab-scale sequencing batch reactor for partial nitrification. The reactor was operated with stepwise increases in the NH sub(4) super(+) loading rate, which resulted in a maximum FA concentration of 29.3 mg-N/L at pH 8.3. Afterwards, FNA was increased by a gradual decrease of pH, reaching its maximum concentration of 4.1 mg-N/L at pH 6.3. Fluorescence in situ hybridization indicated that AOB remained predominant during the operation, achieving specific nitrification rates of 1.04 and 0.99 g-N/g-VSS/day at the highest accumulations of FA and FNA, respectively. These rates were in conjunction with partial nitrification efficiencies of >84%. The N sub(2)O emission factor of oxidized NH sub(4) super(+) was 0.90% at pH 7.0, which was higher than those at pH 8.3 (0.11%) and 6.3 (0.12%), the pHs with the maximum FA and FNA concentrations, respectively. High-throughput sequencing of 16S ribosomal RNA genes showed that increases in FNA drastically changed the predominant AOB species, although increased FA produced no significant changes. This study demonstrates that the FNA concentration and pH are the main drivers that determine the predominant AOB species and N sub(2)O-emission in a partial nitrifying bioreactor.
Background. This study examined the effect of microRNA-125b (miR-125b) on sepsis-induced cardiac dysfunction. Methods. Mouse hearts were transfected with lentivirus expressing miR-125b (LmiR-125b) 7 ...days before cecal ligation and puncture (CLP)–induced sepsis. Cardiac function was examined by echocardiography before and 6 hours after CLP (n = 6/group). Survival was monitored following CLP-induced sepsis (n = 12/group). Results. LmiR-125b transfection significantly attenuated cardiac dysfunction due to CLP-induced sepsis. Fractional shortening and ejection fraction values were significantly (P < .05) higher in the LmiR-125b–treated CLP group than in the untreated CLP group. Survival outcome in LmiR-125b–transfected septic mice was markedly improved, compared with mice with CLP-induced sepsis. Transfection of LmiR-125b into the heart significantly suppressed the expression of ICAM-1 and VCAM-1, decreased the accumulationof of macrophages and neutrophils in the myocardium, and decreased serum levels of tumor necrosis factor α and interleukin 1β by targeting tumor necrosis factor receptor-associated factor 6 (TRAF6)-mediated nuclear factor kB (NF-kB) activation. In addition, sepsis-induced myocardial apoptosis was markedly attenuated by LmiR-125b transfection through suppression of p53, Bax, and Bakl expression. In vitro transfection of endothelial cells with miR-125b mimics attenuate LPS-induced ICAM-1 and VCAM-1 expression by suppressing TRAF6 and NF-kB activation. Conclusions. Increased myocardial miR-125b expression attenuates sepsis-induced cardiac dysfunction and improves survival. miR-125b may be a target for septic cardiomyopathy.
Bacterial processes necessary for adaption to stressful host environments are potential targets for new antimicrobials. Here, we report large-scale transcriptomic analyses of 32 human bacterial ...pathogens grown under 11 stress conditions mimicking human host environments. The potential relevance of the in vitro stress conditions and responses is supported by comparisons with available in vivo transcriptomes of clinically important pathogens. Calculation of a probability score enables comparative cross-microbial analyses of the stress responses, revealing common and unique regulatory responses to different stresses, as well as overlapping processes participating in different stress responses. We identify conserved and species-specific 'universal stress responders', that is, genes showing altered expression in multiple stress conditions. Non-coding RNAs are involved in a substantial proportion of the responses. The data are collected in a freely available, interactive online resource (PATHOgenex).
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