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William M Shafer
In a previous mBio article, Wadsworth and colleagues (mBio 9:e01419-18, 2018, described Neisseria gonorrhoeae isolates that express low levels of azithromycin (Azi) resistance. Whole-genome sequencing and bioinformatic analysis suggested that the isolates had acquired DNA from commensal Neisseria spp. that caused numerous nucleotide changes in the mtr locus, which contains genes for a transcriptional repressor (MtrR) and three proteins (MtrC-MtrD-MtrE) that form a multidrug efflux pump known to export macrolides...
September 11, 2018: MBio
Brandyn R West, Crystal L Moyer, Liam B King, Marnie L Fusco, Jacob C Milligan, Sean Hui, Erica Ollmann Saphire
Only one naturally occurring human antibody has been described thus far that is capable of potently neutralizing all five ebolaviruses. Here we present two crystal structures of this rare, pan-ebolavirus neutralizing human antibody in complex with Ebola virus and Bundibugyo virus glycoproteins (GPs), respectively. The structures delineate the key protein and glycan contacts for binding that are conserved across the ebolaviruses, explain the antibody's unique broad specificity and neutralization activity, and reveal the likely mechanism behind a known escape mutation in the fusion loop region of GP2...
September 11, 2018: MBio
Eleonora Forte, Suchitra Swaminathan, Mark W Schroeder, Jeong Yeon Kim, Scott S Terhune, Mary Hummel
We used the Kasumi-3 model to study human cytomegalovirus (HCMV) latency and reactivation in myeloid progenitor cells. Kasumi-3 cells were infected with HCMV strain TB40/E wt -GFP, flow sorted for green fluorescent protein-positive (GFP+ ) cells, and cultured for various times to monitor establishment of latency, as judged by repression of viral gene expression (RNA/DNA ratio) and loss of virus production. We found that, in the vast majority of cells, latency was established posttranscriptionally in the GFP+ infected cells: transcription was initially turned on and then turned off...
September 11, 2018: MBio
Eva Garmendia, Gerrit Brandis, Diarmaid Hughes
Highly expressed genes are commonly located close to the origin of replication of bacterial chromosomes (OriC). This location skew is thought to reflect selective advantages associated with gene dosage effects during the replication cycle. The expression of constitutively expressed genes can vary up to fivefold based on chromosomal location, but it is not clear what level of variation would occur in naturally regulated operons. We tested the magnitude of the chromosome location effect using EF-Tu ( tufA , tufB ), an abundant protein whose cellular level correlates with, and limits, the maximum growth rate...
September 11, 2018: MBio
Christopher A Gaulke, Holly K Arnold, Ian R Humphreys, Steven W Kembel, James P O'Dwyer, Thomas J Sharpton
Our knowledge of how the gut microbiome relates to mammalian evolution benefits from the identification of gut microbial taxa that are unexpectedly prevalent or unexpectedly conserved across mammals. Such taxa enable experimental determination of the traits needed for such microbes to succeed as gut generalists, as well as those traits that impact mammalian fitness. However, the punctuated resolution of microbial taxonomy may limit our ability to detect conserved gut microbes, especially in cases in which broadly related microbial lineages possess shared traits that drive their apparent ubiquity across mammals...
September 11, 2018: MBio
Danguole Kureisaite-Ciziene, Aravindan Varadajan, Stephen H McLaughlin, Marjolein Glas, Alejandro Montón Silva, Rosa Luirink, Carolin Mueller, Tanneke den Blaauwen, Tom N Grossmann, Joen Luirink, Jan Löwe
Most bacteria and archaea use the tubulin homologue FtsZ as its central organizer of cell division. In Gram-negative Escherichia coli bacteria, FtsZ recruits cytosolic, transmembrane, periplasmic, and outer membrane proteins, assembling the divisome that facilitates bacterial cell division. One such divisome component, FtsQ, a bitopic membrane protein with a globular domain in the periplasm, has been shown to interact with many other divisome proteins. Despite its otherwise unknown function, it has been shown to be a major divisome interaction hub...
September 11, 2018: MBio
Rishi R Trivedi, John A Crooks, George K Auer, Joel Pendry, Ilona P Foik, Albert Siryaporn, Nicholas L Abbott, Zemer Gitai, Douglas B Weibel
The stiffness of bacteria prevents cells from bursting due to the large osmotic pressure across the cell wall. Many successful antibiotic chemotherapies target elements that alter mechanical properties of bacteria, and yet a global view of the biochemistry underlying the regulation of bacterial cell stiffness is still emerging. This connection is particularly interesting in opportunistic human pathogens such as Pseudomonas aeruginosa that have a large (80%) proportion of genes of unknown function and low susceptibility to different families of antibiotics, including beta-lactams, aminoglycosides, and quinolones...
September 11, 2018: MBio
Johannes Westman, Gary Moran, Selene Mogavero, Bernhard Hube, Sergio Grinstein
Macrophages rely on phagosomal acidity to destroy engulfed microorganisms. To survive this hostile response, opportunistic fungi such as Candida albicans developed strategies to evade the acidic environment. C. albicans is polymorphic and able to convert from yeast to hyphae, and this transition is required to subvert the microbicidal activity of the phagosome. However, the phagosomal lumen, which is acidic and nutrient deprived, is believed to inhibit the yeast-to-hypha transition. To account for this apparent paradox, it was recently proposed that C...
September 11, 2018: MBio
Yu-Cheng Lin, William Cole Cornell, Jeanyoung Jo, Alexa Price-Whelan, Lars E P Dietrich
Pseudomonas aeruginosa is the most common cause of chronic, biofilm-based lung infections in patients with cystic fibrosis (CF). Sputum from patients with CF has been shown to contain oxic and hypoxic subzones as well as millimolar concentrations of lactate. Here, we describe the physiological roles and expression patterns of P. aeruginosa lactate dehydrogenases in the contexts of different growth regimes. P. aeruginosa produces four enzymes annotated as lactate dehydrogenases, three of which are known to contribute to anaerobic or aerobic metabolism in liquid cultures...
September 11, 2018: MBio
Gabriel Duette, Pehuen Pereyra Gerber, Julia Rubione, Paula S Perez, Alan L Landay, Suzanne M Crowe, Zhaohao Liao, Kenneth W Witwer, María Pía Holgado, Jimena Salido, Jorge Geffner, Omar Sued, Clovis S Palmer, Matias Ostrowski
Chronic immune activation and inflammation are hallmarks of HIV-1 infection and a major cause of serious non-AIDS events in HIV-1-infected individuals on antiretroviral treatment (ART). Herein, we show that cytosolic double-stranded DNA (dsDNA) generated in infected CD4+ T cells during the HIV-1 replication cycle promotes the mitochondrial reactive oxygen species (ROS)-dependent stabilization of the transcription factor hypoxia-inducible factor 1α (HIF-1α), which in turn, enhances viral replication. Furthermore, we show that induction of HIF-1α promotes the release of extracellular vesicles (EVs)...
September 11, 2018: MBio
Bianca S Heinrich, Zoltan Maliga, David A Stein, Anthony A Hyman, Sean P J Whelan
RNA viruses that replicate in the cell cytoplasm typically concentrate their replication machinery within specialized compartments. This concentration favors enzymatic reactions and shields viral RNA from detection by cytosolic pattern recognition receptors. Nonsegmented negative-strand (NNS) RNA viruses, which include some of the most significant human, animal, and plant pathogens extant, form inclusions that are sites of RNA synthesis and are not circumscribed by a membrane. These inclusions share similarities with cellular protein/RNA structures such as P granules and nucleoli, which are phase-separated liquid compartments...
September 4, 2018: MBio
Wendy Ullmer, Bert L Semler
The cellular mRNA decay protein AUF1 acts as a restriction factor during infection by picornaviruses, including poliovirus, coxsackievirus, and human rhinovirus. AUF1 relocalizes from the nucleus to the cytoplasm during infection by these viruses due to the disruption of nucleocytoplasmic trafficking by viral proteinases. Previous studies have demonstrated that AUF1 binds to poliovirus and coxsackievirus B3 (CVB3) RNA during infection, with binding shown to occur within the internal ribosome entry site (IRES) of the 5' noncoding region (NCR) or the 3' NCR, respectively...
September 4, 2018: MBio
Yi Cao, Robert J Hart, Geetha P Bansal, Nirbhay Kumar
Sexual-stage proteins have a distinct function in the mosquito vector during transmission and also represent targets for the development of malaria transmission-blocking vaccine. P48/45, a leading vaccine candidate, is critical for male gamete fertility and shows >50% similarity across various species of Plasmodium We evaluated functional conservation of P48/45 in Plasmodium vivax and P. berghei with the motivation to establish transgenic P. berghei strains expressing P. vivax P48/45 (Pvs48/45) in an in vivo assay to evaluate the transmission-blocking activity of antibodies elicited by Pvs48/45...
September 4, 2018: MBio
Douglas G Capone
K. Kitzinger et al. (mBio 9:e01186-18, 2018, report the first isolation of a novel nitrite-oxidizing bacterium, " Candidatus Nitrotoga," and provide the first detailed information on the physiology, phylogeny, and characterization of the nitrite-oxidizing system of this genus. The isolate was derived from a wastewater treatment system and exhibits adaptation and tolerance to relatively high levels of nitrite. The origin of its nitrite oxidoreductase is distinct from other known nitrite oxidoreductase (NXR) systems, having arisen either in this organism or by horizontal gene transfer...
September 4, 2018: MBio
C Lori, A Kaczmarczyk, I de Jong, U Jenal
No abstract text is available yet for this article.
September 4, 2018: MBio
Asmaa Tazi, João Ricardo Araujo, Céline Mulet, Ellen T Arena, Giulia Nigro, Thierry Pédron, Philippe J Sansonetti
The gut microbiota contributes to nutrients absorption and metabolism by enterocytes, but the molecular mechanisms involved remain poorly understood, and most conclusions are inferred from studies comparing germfree and conventional animals colonized with diverse bacterial species. We selected two model commensal microorganisms, Escherichia coli and Lactobacillus paracasei , to assess the role of the small-intestinal microbiota in modulating lipid absorption and metabolism by the epithelium. Using an integrated approach encompassing cellular and murine models and combining metabolic parameters measurement, lipid droplet imaging, and gene expression analysis, we demonstrated that under homeostatic conditions, L...
September 4, 2018: MBio
Jan Kampf, Jan Gerwig, Kerstin Kruse, Robert Cleverley, Miriam Dormeyer, Alexander Grünberger, Dietrich Kohlheyer, Fabian M Commichau, Richard J Lewis, Jörg Stülke
Biofilm formation by Bacillus subtilis requires the expression of genes encoding enzymes for extracellular polysaccharide synthesis and for an amyloid-like protein. The master regulator SinR represses all the corresponding genes, and repression of these key biofilm genes is lifted when SinR interacts with its cognate antagonist proteins. The YmdB phosphodiesterase is a recently discovered factor that is involved in the control of SinR activity: cells lacking YmdB exhibit hyperactive SinR and are unable to relieve the repression of the biofilm genes...
September 4, 2018: MBio
Julienne C Kaiser, David E Heinrichs
The branched-chain amino acids (BCAAs [Ile, Leu, and Val]) represent important nutrients in bacterial physiology, with roles that range from supporting protein synthesis to signaling and fine-tuning the adaptation to amino acid starvation. In some pathogenic bacteria, the adaptation to amino acid starvation includes induction of virulence gene expression: thus, BCAAs support not only proliferation during infection, but also the evasion of host defenses. A body of research has accumulated over the years to describe the multifaceted physiological roles of BCAAs and the mechanisms bacteria use to maintain their intracellular levels...
September 4, 2018: MBio
Alison E Mather, Tu Le Thi Phuong, Yunfeng Gao, Simon Clare, Subhankar Mukhopadhyay, David A Goulding, Nhu Tran Do Hoang, Ha Thanh Tuyen, Nguyen Phu Huong Lan, Corinne N Thompson, Nguyen Hoang Thu Trang, Juan Carrique-Mas, Ngo Tri Tue, James I Campbell, Maia A Rabaa, Duy Pham Thanh, Katherine Harcourt, Ngo Thi Hoa, Nguyen Vinh Trung, Constance Schultsz, Gabriel G Perron, John E Coia, Derek J Brown, Chinyere Okoro, Julian Parkhill, Nicholas R Thomson, Nguyen Van Vinh Chau, Guy E Thwaites, Duncan J Maskell, Gordon Dougan, Linda J Kenney, Stephen Baker
Nontyphoidal Salmonella (NTS), particularly Salmonella enterica serovar Typhimurium, is among the leading etiologic agents of bacterial enterocolitis globally and a well-characterized cause of invasive disease (iNTS) in sub-Saharan Africa. In contrast, S  Typhimurium is poorly defined in Southeast Asia, a known hot spot for zoonotic disease with a recently described burden of iNTS disease. Here, we aimed to add insight into the epidemiology and potential impact of zoonotic transfer and antimicrobial resistance (AMR) in S  Typhimurium associated with iNTS and enterocolitis in Vietnam...
September 4, 2018: MBio
Vidhya Vijayakumar, Audrey S Vanhove, Bradley S Pickering, Julie Liao, Braden T Tierney, John M Asara, Roderick Bronson, Paula I Watnick
The Vibrio cholerae phosphoenolpyruvate phosphotransferase system (PTS) is a well-conserved, multicomponent phosphotransfer cascade that coordinates the bacterial response to carbohydrate availability through direct interactions of its components with protein targets. One such component, glucose-specific enzyme IIA (EIIAGlc ), is a master regulator that coordinates bacterial metabolism, nutrient uptake, and behavior by direct interactions with cytoplasmic and membrane-associated protein partners. Here, we show that an amphipathic helix (AH) at the N terminus of V...
September 4, 2018: MBio
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