Cyclic AMP Regulates Bacterial Persistence through Repression of the Oxidative Stress Response and SOS-Dependent DNA Repair in Uropathogenic .

Bacterial persistence is a transient, nonheritable physiological state that provides tolerance to bactericidal antibiotics. The stringent response, toxin-antitoxin modules, and stochastic processes, among other mechanisms, play roles in this phenomenon. How persistence is regulated is relatively ill defined.

A Novel Regulatory Cascade Involving BluR, YcgZ, and Lon Controls the Expression of OmpF Porin.

In , OmpF is an important outer membrane protein, which serves as a passive diffusion pore for small compounds including nutrients, antibiotics, and toxic compounds. OmpF expression responds to environmental changes such as temperature, osmolarity, nutrients availability, and toxic compounds via complex regulatory pathways involving transcriptional and post-transcriptional regulation. Our study identified a new regulatory cascade that controls the expression of OmpF porin.

Triclosan: an Instructive Tale.

The Food and Drug Administration (FDA) recently released a final rule to ban triclosan and 18 other antimicrobial chemicals from soaps. We applaud this rule specifically because of the associated risks that triclosan poses to the spread of antibiotic resistance throughout the environment. This persistent chemical constantly stresses bacteria to adapt, and behavior that promotes antibiotic resistance needs to be stopped immediately when the benefits are null.

Transposon-Sequencing Analysis Unveils Novel Genes Involved in the Generation of Persister Cells in Uropathogenic Escherichia coli.

Persister cells are highly tolerant to different antibiotics and are associated with relapsing infections. In order to understand this phenomenon further, we exposed a transposon library to a lethal concentration of ampicillin, and mutants that survived were identified by transposon sequencing (Tn-Seq). We determined that mutations related to carbon metabolism, cell envelope (cell wall generation and membrane proteins), and stress response have a role in persister cell generation.

Rapid radiation in bacteria leads to a division of labour.

The division of labour is a central feature of the most sophisticated biological systems, including genomes, multicellular organisms and societies, which took millions of years to evolve. Here we show that a well-organized and robust division of labour can evolve in a matter of days. Mutants emerge within bacterial colonies and work with the parent strain to gain new territory.

Does use of the polyene natamycin as a food preservative jeopardise the clinical efficacy of amphotericin B? A word of concern.

Natamycin is a poorly soluble, polyene macrolide antifungal agent used in the food industry for the surface treatment of cheese and sausages. This use is not of safety concern. However, highly soluble natamycin-cyclodextrin inclusion complexes have been developed for the protection of beverages.

Importance of positioning for microbial evolution.

Microbes commonly live in dense surface-attached communities where cells layer on top of one another such that only those at the edges have unimpeded access to limiting nutrients and space. Theory predicts that this simple spatial effect, akin to plants competing for light in a forest, generates strong natural selection on microbial phenotypes. However, we require direct empirical tests of the importance of this spatial structuring.

Amino acid residues involved in inactivation of the Escherichia coli multidrug resistance repressor MarR by salicylate, 2,4-dinitrophenol, and plumbagin.

MarR is the dedicated autorepressor of the marRAB operon found in seven genera of the Enterobacteraceae. The MarA transcriptional regulator directly activates numerous genes involved in multidrug resistance and other environmental responses. MarR is inactivated by certain phenolic ligands, such as salicylate, by an unknown mechanism.

Regulation of acrAB expression by cellular metabolites in Escherichia coli.

Objectives: Multidrug efflux pumps mediate resistance to antibiotics and other toxic compounds. We studied the role of AcrAB-TolC, the main efflux pump in Escherichia coli, in regulating gene expression.

Methods: Deletion mutants, an acrABp-lacZ fusion and reverse transcription-real-time quantitative PCR experiments were used to study the role of AcrAB-TolC and metabolism in regulating gene expression of the acrAB operon and its transcriptional regulators.

Mechanism of action of the novel aminomethylcycline antibiotic omadacycline.

Omadacycline is a novel first-in-class aminomethylcycline with potent activity against important skin and pneumonia pathogens, including community-acquired methicillin-resistant Staphylococcus aureus (MRSA), β-hemolytic streptococci, penicillin-resistant Streptococcus pneumoniae, Haemophilus influenzae, and Legionella. In this work, the mechanism of action for omadacycline was further elucidated using a variety of models. Functional assays demonstrated that omadacycline is active against strains expressing the two main forms of tetracycline resistance (efflux and ribosomal protection).

The contribution of PmrAB to the virulence of a clinical isolate of Escherichia coli.

Previous data from our laboratory suggest a relationship between increased pmrAB expression and virulence in an Escherichia coli mouse infection model of pyelonephritis. Competitive infections with wild type and pmrAB mutants showed that disruption of pmrAB caused decreased persistence of E. coli within the mouse kidney.

Pleiotropic effects of GacA on Pseudomonas fluorescens Pf0-1 in vitro and in soil.

Pseudomonas species can exhibit phenotypic variation resulting from gacS or gacA mutation. P. fluorescens Pf0-1 is a gacA mutant and exhibits pleiotropic changes following the introduction of a functional allele.

The 216-bp marB gene of the marRAB operon in Escherichia coli encodes a periplasmic protein which reduces the transcription rate of marA.

The marRAB operon is conserved in seven genera of enteric bacteria (Escherichia, Shigella, Klebsiella, Enterobacter, Salmonella, Cronobacter, and Citrobacter). MarA is a transcriptional regulator affecting many genes involved in resistance to stresses, and MarR is an autorepressor of the operon, but a role for the marB gene has been unclear. A recent work reported that deletion of marB causes resistance to certain stresses and increases the amount of marA transcript.

Mutational analysis of the multiple-antibiotic resistance regulator MarR reveals a ligand binding pocket at the interface between the dimerization and DNA binding domains.

The Escherichia coli regulator MarR represses the multiple-antibiotic resistance operon marRAB and responds to phenolic compounds, including sodium salicylate, which inhibit its activity. Crystals obtained in the presence of a high concentration of salicylate indicated two possible salicylate sites, SAL-A and SAL-B. However, it was unclear whether these sites were physiologically significant or were simply a result of the crystallization conditions.

Honeybees and tetracycline resistance.

Like animals and people, insects can serve as both collectors and disseminators of antibiotic resistance genes, as exquisitely demonstrated by a recent study (B. Tian, N. H.

Involvement of MarR and YedS in carbapenem resistance in a clinical isolate of Escherichia coli from China.

A carbapenem-resistant clinical isolate of Escherichia coli, which lacked OmpF and OmpC porins, carried a marR mutation and expressed a functional yedS, a normally nontranslated gene. MarR and YedS are described here as having effects on the ability of this strain to resist carbapenems. Additionally, expression of YedS was regulated by the small RNA MicF in a MarA-dependent way.

The frequency of antibiotic-resistant bacteria in homes differing in their use of surface antibacterial agents.

Antibacterial agents are common in household cleaning and personal care products, but their long-range impacts on commensal and pathogenic household bacteria are largely unknown. In a one-time survey of 38 households from Boston, MA [19] and Cincinnati, OH [18], 13 kitchen and bathroom sites were sampled for total aerobic bacteria and screened for gram phenotype and susceptibility to six antibiotic drug families. The overall bacterial titers of both user (2 or more antibacterial cleaning or personal care products) and non-user (0 or 1 product) rooms were similar with sponges and sink drains consistently showing the highest overall titers and relatively high titers of antibiotic-resistant bacteria.

Regulation of polyphosphate kinase production by antisense RNA in Pseudomonas fluorescens Pf0-1.

Pseudomonas spp. adapt rapidly to environmental fluctuations. Loss or overproduction of polyphosphate reduces the fitness of Pseudomonas fluorescens Pf0-1, indicating the importance of the fine-tuning of polyphosphate production.

Novel genes involved in Pseudomonas fluorescens Pf0-1 motility and biofilm formation.

AdnA in Pseudomonas fluorescens, an ortholog of FleQ in P. aeruginosa, regulates both motility and flagellum-mediated attachment to various surfaces. A whole-genome microarray determined the AdnA transcriptome by comparing the gene expression pattern of wild-type Pf0-1 to that of Pf0-2x (adnA deletion mutant) in broth culture.

SoxS increases the expression of the zinc uptake system ZnuACB in an Escherichia coli murine pyelonephritis model.

Paralogous transcriptional regulators MarA, Rob, and SoxS act individually and together to control expression of more than 80 Escherichia coli genes. Deletion of marA, rob, and soxS from an E. coli clinical isolate prevents persistence beyond 2 days postinfection in a mouse model of pyelonephritis.

The history of the tetracyclines.

The history of the tetracyclines involves the collective contributions of thousands of dedicated researchers, scientists, clinicians, and business executives over the course of more than 60 years. Discovered as natural products from actinomycetes soil bacteria, the tetracyclines were first reported in the scientific literature in 1948. They were noted for their broad spectrum antibacterial activity and were commercialized with clinical success beginning in the late 1940s to the early 1950s.

Yersinia pestis AcrAB-TolC in antibiotic resistance and virulence.

The efflux pump AcrAB is important in the antibiotic resistance and virulence of several pathogenic bacteria. We report that deletion of the Yersinia pestis AcrAB-TolC homolog leads to increased susceptibility to diverse substrates, including, though unlike in Escherichia coli, the aminoglycosides. Neither is the Y.

Food animals and antimicrobials: impacts on human health.

Antimicrobials are valuable therapeutics whose efficacy is seriously compromised by the emergence and spread of antimicrobial resistance. The provision of antibiotics to food animals encompasses a wide variety of nontherapeutic purposes that include growth promotion. The concern over resistance emergence and spread to people by nontherapeutic use of antimicrobials has led to conflicted practices and opinions.