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Elise Iracane, Paul D Donovan, Mihaela Ola, Geraldine Butler, Linda M Holland
The unfolded protein response (UPR) in the endoplasmic reticulum (ER) is well conserved in eukaryotes from metazoa to yeast. The transcription factor HAC1 is a major regulator of the UPR in many eukaryotes. Deleting HAC1 in the yeast Candida parapsilosis rendered cells more sensitive to DTT, a known inducer of the UPR. The deletion strain was also sensitive to Congo red, calcofluor white, and the antifungal drug ketoconazole, indicating that HAC1 has a role in cell wall maintenance. Transcriptomic analysis revealed that treatment of the wild type with DTT resulted in the increased expression of 368 genes...
November 7, 2018: MSphere
Flávio Lemos Matassoli, Ihid Carneiro Leão, Bruno Braz Bezerra, Richard B Pollard, Dieter Lütjohann, James E K Hildreth, Luciana Barros de Arruda
Monocytes from HIV-infected patients produce increased levels of inflammatory cytokines, which are associated with chronic immune activation and AIDS progression. Chronic immune activation is often not restored even in patients showing viral suppression under ART. Therefore, new therapeutic strategies to control inflammation and modulate immune activation are required. Hydroxypropyl-beta-cyclodextrin (HP-BCD) is a cholesterol-sequestering agent that has been reported to be safe for human use in numerous pharmaceutical applications and that has been shown to inactivate HIV in vitro and to control SIV infection in vivo Since cellular cholesterol content or metabolism has been related to altered cellular activation, we evaluated whether HP-BCD treatment could modulate monocyte response to inflammatory stimuli...
November 7, 2018: MSphere
Kate A Worthing, Sybille Schwendener, Vincent Perreten, Sugiyono Saputra, Geoffrey W Coombs, Stanley Pang, Mark R Davies, Sam Abraham, Darren J Trott, Jacqueline M Norris
We examined the oxacillin resistance phenotype and genomic structure of staphylococcal cassette chromosome mec (SCC mec ) elements from 77 veterinary methicillin-resistant Staphylococcus pseudintermedius (MRSP) isolates. Isolates were characterized by oxacillin broth microdilution, whole-genome sequencing, and bioformatics analysis. Five previously described SCC mec elements, and a sixth novel element, were identified: SCC mec III (also known as II-III), ΨSCC mec 57395 , and SCC mec NA45 (a SCC mec VII variant), all previously described in MRSP, and SCC mec IVg and SCC mec VT , previously described in both methicillin-resistant Staphylococcus aureus (MRSA) and MRSP...
November 7, 2018: MSphere
K Shamsur Rahman, Toni Darville, Harold C Wiesenfeld, Sharon L Hillier, Bernhard Kaltenboeck
Sensitive and specific detection of anti- Chlamydia trachomatis antibodies in standard enzyme-linked immunosorbent assays (ELISAs) is compromised by cross-reactivity and poor sensitivity of classical C. trachomatis antigens. Previously, we discovered 48 strongly reactive peptide antigens of C. trachomatis -specific B-cell epitopes from 21 immunodominant proteins. By comprehensive individual testing of 11 top-ranked peptide antigens, we found very high sensitivity and specificity for detection of anti- C. trachomatis antibodies in chemiluminescent ELISAs...
November 7, 2018: MSphere
A Sivertsen, J Janice, T Pedersen, T M Wagner, J Hegstad, K Hegstad
Enterococcus faecium has a highly variable genome prone to recombination and horizontal gene transfer. Here, we have identified a novel genetic island with an insertion locus and mobilization genes similar to those of staphylococcus cassette chromosome elements SCC mec This novel element termed the enterococcus cassette chromosome (ECC) element was located in the 3' region of rlmH and encoded large serine recombinases ccrAB similar to SCC mec Horizontal transfer of an ECC element termed ECC:: cat containing a knock-in cat chloramphenicol resistance determinant occurred in the presence of a conjugative rep pLG1 plasmid...
November 7, 2018: MSphere
Xiaoyuan Yuan, Kai Meng, Yuxia Zhang, Lihong Qi, Wu Ai, Youling Wang
In 2017, a new type of goose-origin astrovirus (GoAstV) that is completely different from previously identified avian astroviruses (which have only 30.0% to 50.5% homology with GoAstV) has been isolated from diseased geese in China. This disease can cause joint swelling in sick geese, and the anatomy shows a clear precipitation of urate in the kidney. The rate of death and culling can reach more than 30%, revealing the disease's severe pathogenicity. To quickly and accurately diagnose the newly emerging disease, we established a highly specific reverse transcription-quantitative PCR (RT-qPCR) method of detecting GoAstV...
November 7, 2018: MSphere
Flor M Munoz, Pierre Van Damme, Ener Dinleyici, Ed Clarke, Beate Kampmann, Paul T Heath, Ofer Levy, Elke Leuridan, Clare Cutland, Ajoke Sobanjo-Ter Meulen, Arnaud Marchant
Prevention of serious infections in pregnant mothers, newborns, and young infants through immunization during pregnancy and in early life has the potential to further reduce maternal and neonatal morbidity and mortality worldwide. In the past decade, research in this field has advanced substantially, from the understanding of the biology and immunology of pregnancy and early life, to the active development of several candidate vaccines, for which challenges and opportunities for global implementation are under consideration...
November 7, 2018: MSphere
Xiongfeng Dai, Zichu Shen, Yiheng Wang, Manlu Zhu
Bacterial cells need to coordinate the cell cycle with biomass growth to maintain cell size homeostasis. For fast-growing bacterial species like Escherichia coli and Bacillus s ubtilis , it is well-known that cell size exhibits a strong dependence on the growth rate under different nutrient conditions (known as the nutrient growth law). However, cell size changes little with slow growth (doubling time of >90 min) for E. coli , posing the interesting question of whether slow-growing bacteria species also observe the nutrient growth law...
November 7, 2018: MSphere
Ezequiel Valguarnera, Nichollas E Scott, Philippe Azimzadeh, Mario F Feldman
Outer membrane vesicles (OMVs) are spherical structures derived from the outer membranes (OMs) of Gram-negative bacteria. Bacteroides spp. are prominent components of the human gut microbiota, and OMVs produced by these species are proposed to play key roles in gut homeostasis. OMV biogenesis in Bacteroides is a poorly understood process. Here, we revisited the protein composition of Bacteroides thetaiotaomicron OMVs by mass spectrometry. We confirmed that OMVs produced by this organism contain large quantities of glycosidases and proteases, with most of them being lipoproteins...
November 7, 2018: MSphere
Taylor K S Richter, Tracy H Hazen, Diana Lam, Christian L Coles, Jessica C Seidman, Yaqi You, Ellen K Silbergeld, Claire M Fraser, David A Rasko
The stability of the Escherichia coli populations in the human gastrointestinal tract is not fully appreciated, and represents a significant knowledge gap regarding gastrointestinal community structure, as well as resistance to incoming pathogenic bacterial species and antibiotic treatment. The current study examines the genomic content of 240 Escherichia coli isolates from 30 children, aged 2 to 35 months old, in Tanzania. The E. coli strains were isolated from three time points spanning a six-month time period, with and without antibiotic treatment...
November 7, 2018: MSphere
Jessica Loraine, Eva Heinz, Jessica De Sousa Almeida, Oleksandr Milevskyy, Supayang P Voravuthikunchai, Potjanee Srimanote, Pattarachai Kiratisin, Nicholas R Thomson, Peter W Taylor
The capacity to resist the bactericidal action of complement (C') is a strong but poorly understood virulence trait in Klebsiella spp. Killing requires activation of one or more C' pathways, assembly of C5b-9 membrane attack complexes (MACs) on the surface of the outer membrane (OM), and penetration of MACs into the target bilayer. We interrogated whole-genome sequences of 164 Klebsiella isolates from three tertiary hospitals in Thailand for genes encoding surface-located macromolecules considered to play a role in determination of C' resistance...
November 7, 2018: MSphere
Raghav Vij, Radames J B Cordero, Arturo Casadevall
Cryptococcus neoformans is an environmental pathogenic fungus with a worldwide geographical distribution that is responsible for hundreds of thousands of human cryptococcosis cases each year. During infection, the yeast undergoes a morphological transformation involving capsular enlargement that increases microbial volume. To understand the factors that play a role in environmental dispersal of C. neoformans and C. gattii , we evaluated the cell density of Cryptococcus using Percoll isopycnic gradients. We found differences in the cell densities of strains belonging to C...
November 7, 2018: MSphere
Rachael L Hardison, Derek R Heimlich, Alistair Harrison, Wandy L Beatty, Sarah Rains, M Arthur Moseley, J Will Thompson, Sheryl S Justice, Kevin M Mason
No abstract text is available yet for this article.
October 31, 2018: MSphere
Zeinab Mamouei, Abdullah Alqarihi, Shakti Singh, Shuying Xu, Michael K Mansour, Ashraf S Ibrahim, Priya Uppuluri
Invasive fungal infections due to Candida albicans , Aspergillus fumigatus , and Cryptococcus neoformans constitute a substantial threat to hospitalized immunocompromised patients. Further, the presence of drug-recalcitrant biofilms on medical devices and emergence of drug-resistant fungi, such as Candida auris , introduce treatment challenges with current antifungal drugs. Worse, currently there is no approved drug capable of obviating preformed biofilms, which increase the chance of infection relapses. Here, we screened a small-molecule New Prestwick Chemical Library, consisting of 1,200 FDA-approved off-patent drugs against C...
October 31, 2018: MSphere
Christine Clayton
Salivarian trypanosomes grow in mammals, where they depend on glucose, and as procyclic forms in tsetse flies, where they metabolize proline. Differentiation of bloodstream forms to nongrowing stumpy forms, and to procyclic forms, has been studied extensively, but reconciling the results is tricky because investigators have used parasites with various differentiation competences and different media for procyclic-form culture. Standard protocols include lowering the temperature to 27°C, adding a tricarboxylic acid, and transferring the parasites to high-proline medium, often including glucose...
October 31, 2018: MSphere
Mina Mostafavi, Lisha Wang, Lili Xie, Kenneth T Takeoka, Daryl L Richie, Fergal Casey, Alexey Ruzin, William S Sawyer, Christopher M Rath, Jun-Rong Wei, Charles R Dean
Tight coordination of inner and outer membrane biosynthesis is very important in Gram-negative bacteria. Biosynthesis of the lipid A moiety of lipopolysaccharide, which comprises the outer leaflet of the outer membrane has garnered interest for Gram-negative antibacterial discovery. In particular, several potent inhibitors of LpxC (the first committed step of the lipid A pathway) are described. Here we show that serial passaging of Klebsiella pneumoniae in increasing levels of an LpxC inhibitor yielded mutants that grew only in the presence of the inhibitor...
October 31, 2018: MSphere
Simon A M Underhill, Robert C Shields, Justin R Kaspar, Momin Haider, Robert A Burne, Stephen J Hagen
Entry into genetic competence in streptococci is controlled by ComX, an alternative sigma factor for genes that enable the import of exogenous DNA. In Streptococcus mutans , the immediate activator of comX is the ComRS quorum system. ComS is the precursor of XIP, a seven-residue peptide that is imported into the cell and interacts with the cytosolic receptor ComR to form a transcriptional activator for both comX and comS Although intercellular quorum signaling by ComRS has been demonstrated, observations of bimodal expression of comX suggest that comRS may also function as an intracellular feedback loop, activating comX without export or detection of extracellular XIP...
October 31, 2018: MSphere
Ryan P Trombetta, Paul M Dunman, Edward M Schwarz, Stephen L Kates, Hani A Awad
Drug repurposing offers an expedited and economical route to develop new clinical therapeutics in comparison to traditional drug development. Growth-based high-throughput screening is concomitant with drug repurposing and enables rapid identification of new therapeutic uses for investigated drugs; however, this traditional method is not compatible with microorganisms with abnormal growth patterns such as Staphylococcus aureus small-colony variants (SCV). SCV subpopulations are auxotrophic for key compounds in biosynthetic pathways, which result in low growth rate...
October 31, 2018: MSphere
Yijian Qiu, Jillian E Milanes, Jessica A Jones, Rooksana E Noorai, Vijay Shankar, James C Morris
The African trypanosome has evolved mechanisms to adapt to changes in nutrient availability that occur during its life cycle. During transition from mammalian blood to insect vector gut, parasites experience a rapid reduction in environmental glucose. Here we describe how pleomorphic parasites respond to glucose depletion with a focus on parasite changes in energy metabolism and growth. Long slender bloodstream form parasites were rapidly killed as glucose concentrations fell, while short stumpy bloodstream form parasites persisted to differentiate into the insect-stage procyclic form parasite...
October 31, 2018: MSphere
Kiranmai Bhatt, Henrique Machado, Nuno S Osório, Jeremy Sousa, Filipa Cardoso, Carlos Magalhães, Bing Chen, Mei Chen, John Kim, Albel Singh, Catarina M Ferreira, António G Castro, Egidio Torrado, William R Jacobs, Apoorva Bhatt, Margarida Saraiva
Nonribosomal peptide synthases produce short peptides in a manner that is distinct from classical mRNA-dependent ribosome-mediated translation. The Mycobacterium tuberculosis genome harbors a nonribosomal peptide synthase gene, nrp , which is part of a gene cluster proposed to be involved in the biosynthesis of isonitrile lipopeptides. Orthologous clusters are found in other slow-growing pathogenic mycobacteria and actinomycetes. To probe the role of the nrp gene in infection, we generated an nrp deletion mutant in M...
October 31, 2018: MSphere
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