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Current Opinion in Microbiology

Erez Mills, Roi Avraham
Most of our understanding of the host-bacterium interaction has come from studies of bulk populations. In reality, highly adaptable and dynamic host cells and bacteria engage in complex, diverse interactions. This complexity necessarily limits the depth of understanding that can be gained with bulk population measurements. Here, we will review the merit of single cell analysis to characterize this diversity that can trigger heterogeneous outcomes. We will discuss heterogeneity of bacterial and host populations, differences in host microenvironments, technological advances that facilitate the analysis of rare subpopulations, and the potential relevance of these subpopulations to infection outcomes...
February 16, 2017: Current Opinion in Microbiology
Olga Soutourina
Clostridium difficile (CD)-associated diarrhoea is currently the most prevalent nosocomial diarrhoea worldwide. Many characteristics of CD pathogenicity remain poorly understood. Recent data strongly indicate the importance of an RNA network for the control of gene expression in CD. More than 200 regulatory RNAs have been identified by deep sequencing and targeted approaches, including Hfq-dependent trans riboregulators, cis-antisense RNAs, CRISPR RNAs, and c-di-GMP-responsive riboswitches. These regulatory RNAs are involved in the control of major processes in the CD infection cycle, for example motility, biofilm formation, adhesion, sporulation, stress response, and defence against bacteriophages...
February 16, 2017: Current Opinion in Microbiology
Antoine-Emmanuel Saliba, Sara C Santos, Jörg Vogel
Understanding how bacteria cause disease requires knowledge of which genes are expressed and how they are regulated during infection. While RNA-seq is now a routine method for gene expression analysis in bacterial pathogens, the past years have also witnessed a surge of novel RNA-seq based approaches going beyond standard mRNA profiling. These include variations of the technique to capture post-transcriptional networks controlled by small RNAs and to discover associated RNA-binding proteins in the pathogen itself...
February 16, 2017: Current Opinion in Microbiology
Manuel Pazos, Katharina Peters, Waldemar Vollmer
In Gram-negative bacteria such as Escherichia coli the peptidoglycan sacculus resides in the periplasm, a compartment that experiences changes in pH value, osmolality, ion strength and other parameters depending on the cell's environment. Hence, the cell needs robust peptidoglycan growth mechanisms to grow and divide under different conditions. Here we propose a model according to which the cell achieves robust peptidoglycan growth by employing dynamic multi-protein complexes, which assemble with variable composition from freely diffusing sets of peptidoglycan synthases, hydrolases and their regulators, whereby the composition of the active complexes depends on the cell cycle state - cell elongation or division - and the periplasmic growth conditions...
February 15, 2017: Current Opinion in Microbiology
Casey C Fowler, Shu-Jung Chang, Xiang Gao, Tobias Geiger, Gabrielle Stack, Jorge E Galán
Typhoid toxin is a unique A2B5 exotoxin and an important virulence factor for Salmonella Typhi, the cause of typhoid fever. In the decade since its initial discovery, great strides have been made in deciphering the unusual biological program of this toxin, which is fundamentally different from related toxins in many ways. Purified typhoid toxin administered to laboratory animals causes many of the symptoms of typhoid fever, suggesting that typhoid toxin is a central factor in this disease. Further advances in understanding the biology of this toxin will help guide the development of badly needed diagnostics and therapeutic interventions that target this toxin to detect, prevent or treat typhoid fever...
February 14, 2017: Current Opinion in Microbiology
Julien Herrou, Sean Crosson, Aretha Fiebig
Sensor histidine kinases regulate adaptive cellular responses to changes in the chemical or physical state of the environment. HWE/HisKA2-family kinases comprise a subset of histidine kinases that is defined by unique sequence motifs in both the catalytic and non-catalytic regions. Recent crystal structures have defined conserved intramolecular interactions that inform models of kinase regulation that are unique to the HWE/HisKA2 superfamily. Emerging genetic, biochemical and genomic data indicate that, unlike typical histidine kinases, HWE/HisKA2 kinases do not generally signal via classical DNA-binding response regulators...
February 10, 2017: Current Opinion in Microbiology
Ellen L Zechner
Environmental and intrinsic factors that alter microbiota structure can trigger aberrant immune responses. The resulting states of dysbiosis take many forms characterized by overrepresentation of pro-inflammatory organisms and pathobionts and loss of beneficial commensals further aggravating the inflammatory state. The pathogenic potential of the dysbiotic community can be linked to specific organisms in some cases but accumulating evidence suggests that intestinal inflammatory diseases are driven by collective functions of highly variable polymicrobial communities...
February 9, 2017: Current Opinion in Microbiology
Aoife M Colgan, Andrew Ds Cameron, Carsten Kröger
Host-pathogen interactions are exceedingly complex because they involve multiple host tissues, often occur in the context of normal microflora, and can span diverse microenvironments. Although decades of gene expression studies have provided detailed insights into infection processes, technical challenges have restricted experiments to single pathogenic species or host tissues. RNA-sequencing (RNA-seq) has revolutionized the study of gene expression because in addition to quantifying transcriptional output, it allows detection and characterization of all transcripts in a genome...
February 9, 2017: Current Opinion in Microbiology
Kayley H Schulmeyer, Timothy L Yahr
Type III secretion systems (T3SS) serve as a primary anti-host defense mechanism for many Gram-negative plant and animal pathogens. T3SS production is tightly controlled and activated by host-associated signals. Although transcriptional responses represent a significant component of the activation cascade, recent studies have uncovered diverse post-transcriptional mechanisms that also contribute to T3SS production. Targets for post-transcriptional control are often AraC/XylS transcription factors that promote T3SS gene expression...
February 9, 2017: Current Opinion in Microbiology
Jenna G Conner, David Zamorano-Sánchez, Jin Hwan Park, Holger Sondermann, Fitnat H Yildiz
The second messenger nucleotide cyclic dimeric guanosine monophosphate (c-di-GMP) governs many cellular processes in the facultative human pathogen Vibrio cholerae. This organism copes with changing environmental conditions in aquatic environments and during transitions to and from human hosts. Modulation of c-di-GMP allows V. cholerae to shift between motile and sessile stages of life, thus allowing adaptation to stressors and environmental conditions during its transmission cycle. The V. cholerae genome encodes a large set of proteins predicted to degrade and produce c-di-GMP...
February 4, 2017: Current Opinion in Microbiology
Zoya Ignatova, Franz Narberhaus
RNA folds into intricate structures. Recent discoveries using next-generation sequencing (NGS) approaches have revealed unprecedented structural complexity with a pivotal role in regulating RNA function and stability. Here, we present new discoveries from the transcriptome-wide determination of RNA structuromes in bacteria and discuss emerging concepts in the role of mRNA structures in regulating transcription, translation and degradation. We also provide critical viewpoints on the use of NGS approaches for elucidating of RNA structuromes at the systems level...
February 1, 2017: Current Opinion in Microbiology
Taylor B Updegrove, Kumaran S Ramamurthi
Bacterial cells are highly organized at a molecular level. Understanding how specific proteins localize to their proper subcellular address has been a major challenge in bacterial cell biology. One mechanism, which appears to be increasingly more common, is the use of 'geometric cues' for protein localization. In this model, certain shape-sensing proteins recognize, and preferentially embed into, either negatively or positively curved (concave or convex, respectively) membranes. Here, we review examples of bacterial proteins that reportedly localize by sensing geometric cues and highlight emerging mechanistic understandings of how proteins may recognize subtle differences in membrane curvature...
January 19, 2017: Current Opinion in Microbiology
Alexandre Persat
Bacteria rapidly adapt to changes in their environment by leveraging sensing systems that permanently probe their surroundings. One common assumption is that such systems are responsive to signals that are chemical in nature. Yet, bacteria frequently experience changes in mechanical forces, for example as they transition from planktonic to sessile states. Do single bacteria actively sense and respond to mechanical forces? I here briefly review evidence indicating that bacteria actively respond to mechanical stimuli, and along concisely describe their intricate machinery enabling the transduction of force into biochemical activity...
January 6, 2017: Current Opinion in Microbiology
Ashira Lubkin, Victor J Torres
Pathogenic bacteria use the bloodstream as a highway for getting around the body, and thus have to find ways to enter and exit through the endothelium. Many bacteria approach this problem by producing toxins that can breach the endothelial barrier through diverse creative mechanisms, including directly killing endothelial cells (ECs), weakening the cytoskeleton within ECs, and breaking the junctions between ECs. Toxins can also modulate the immune response by influencing endothelial biology, and can modulate endothelial function by influencing the response of leukocytes...
December 22, 2016: Current Opinion in Microbiology
Rebecca L Lamason, Matthew D Welch
Subversion of the host actin cytoskeleton is a critical virulence mechanism used by a variety of intracellular bacterial pathogens during their infectious life cycles. These pathogens manipulate host actin to promote actin-based motility and coordinate motility with cell-to-cell spread. Growing evidence suggests that the tactics employed by pathogens are surprisingly diverse. Here, we review recent advances suggesting that bacterial surface proteins exhibit divergent biochemical mechanisms of actin polymerization and recruit distinct host protein networks to drive motility, and that bacteria deploy secreted effector proteins that alter host cell mechanotransduction pathways to enable spread...
December 17, 2016: Current Opinion in Microbiology
Andrew J Hryckowian, Kali M Pruss, Justin L Sonnenburg
It is widely accepted that Clostridium difficile exploits dysbiosis and leverages inflammation to thrive in the gut environment, where it can asymptomatically colonize humans or cause a toxin-mediated disease ranging in severity from frequent watery diarrhea to pseudomembranous colitis or toxic megacolon. Here, we synthesize recent findings from the gut microbiota and enteric pathogenesis fields to inform the next steps toward a better understanding of C. difficile infection (CDI). In this review, we present a model in which the lifestyle of C...
December 17, 2016: Current Opinion in Microbiology
Lara J Kohler, Craig R Roy
Eukaryotic cells use autophagy to break down and recycle components such as aggregated proteins and damaged organelles. Research in the past decade, particularly using Salmonella enterica serovar Typhimurium as a model pathogen, has revealed that autophagy can also target invading intracellular bacterial pathogens for degradation. However, many bacterial pathogens have evolved mechanisms that allow for evasion of the autophagic pathway, such as motility or direct and irreversible cleavage of proteins that comprise the autophagic machinery...
December 13, 2016: Current Opinion in Microbiology
Lauren O Bakaletz
Preceding or concurrent viral respiratory tract infection can predispose to secondary bacterial co-infection throughout the airway. The mechanisms by which viruses promote these superinfections are diverse and replete. Whereas we understand much as to how viruses damage the airway and dysregulate both innate and acquired immune responses which, in turn, supports bacterial growth, adherence and invasion into normally sterile sites within the respiratory tract, new information regarding these co-infections is being gained from recent advances in microbiome research and our enhanced appreciation of the contribution of bacterial biofilms, among others...
December 7, 2016: Current Opinion in Microbiology
Karen L Adair, Angela E Douglas
The composition of many host-associated microbial communities is characterized by seemingly contradictory features: strong selection for specific taxa by the host, but substantial variability among hosts and over time within one host. Recent advances have revealed that both deterministic and stochastic processes operating across multiple spatial scales shape the composition of host-associated microbial communities. Although most research has focused on deterministic processes within individual hosts, the microbiota within each host is increasingly recognized to contribute to a wider metacommunity maintained by transmission between individual hosts and dispersal between host-associated and free-living microbial communities...
November 28, 2016: Current Opinion in Microbiology
Hiroshi Ashida, Chihiro Sasakawa
Ubiquitination is a crucial post-translational protein modification involved in regulation of various cellular processes in eukaryotes. In particular, ubiquitination is involved in multiple aspects of bacterial infection and host defense mechanisms. In parallel with the identification of ubiquitination as a component of host defense systems, recently accumulated evidence shows that many bacterial pathogens exploit host ubiquitin systems to achieve successful infection. Here, we highlight the strategies by which bacteria subvert host ubiquitin systems by mimicking E3 ubiquitin ligase activity...
November 28, 2016: Current Opinion in Microbiology
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