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Cellular Microbiology

Jessica Quintin
No abstract text is available yet for this article.
July 18, 2018: Cellular Microbiology
Duncan Wilson
No abstract text is available yet for this article.
July 18, 2018: Cellular Microbiology
Dorothy Truong, Kirsten C Boddy, Veronica Canadien, Danielle Brabant, Gregory D Fairn, Vanessa M D'Costa, Etienne Coyaud, Brian Raught, Dolores Perez-Sala, Wei Sun Park, Won Do Heo, Sergio Grinstein, John H Brumell
Salmonella uses type 3 secretion systems (T3SS) to deliver virulence factors, called effectors, into host cells during infection. The T3SS effectors promote invasion into host cells and the generation of a replicative niche. SopB is a T3SS effector that plays an important role in Salmonella pathogenesis through its lipid phosphatase activity. Here we show that SopB mediates the recruitment of Rho GTPases (RhoB, RhoD, RhoH, and RhoJ) to bacterial invasion sites. RhoJ contributes to Salmonella invasion, and RhoB and RhoH play an important role in Akt activation...
July 16, 2018: Cellular Microbiology
Nidhish Francis, Babatunde A Ayodele, Neil M O'Brien-Simpson, Walter Birchmeier, Robert N Pike, Charles N Pagel, Eleanor J Mackie
Chronic periodontitis is characterised by gingival inflammation and alveolar bone loss. A major aetiological agent is Porphyromonas gingivalis, which secretes proteases that activate protease-activated receptor-2 (PAR2 ). PAR2 expressed on oral keratinocytes is activated by proteases released by P. gingivalis, inducing secretion of interleukin-6 (IL-6), and global knockout of PAR2 prevents bone loss and inflammation in a periodontal disease model in mice. To test the hypothesis that PAR2 expressed on gingival keratinocytes is required for periodontal disease pathology, keratinocyte-specific PAR2 -null mice were generated using K14-Cre targeted deletion of the PAR2 gene (F2rl1)...
July 16, 2018: Cellular Microbiology
Sadri Znaidi, Lasse van Wijlick, Arturo Hernández Cervantes, Natacha Sertour, Jean-Luc Desseyn, Frédéric Vincent, Ralitsa Atanassova, Valérie Gouyer, Carol A Munro, Sophie Bachellier-Bassi, Frédéric Dalle, Thierry Jouault, Marie-Elisabeth Bougnoux, Christophe d'Enfert
Candida albicans is part of the human gastrointestinal (GI) microbiota. To better understand how C. albicans efficiently establishes GI colonization, we competitively challenged growth of 572 signature-tagged strains (~10% genome coverage), each conditionally overexpressing a single gene, in the murine gut. We identified CRZ2, a transcription factor whose overexpression and deletion respectively increased and decreased early GI colonization. Using clues from genome-wide expression and gene-set enrichment analyses, we found that the optimal activity of Crz2p occurs under hypoxia at 37°C, as evidenced by both phenotypic and transcriptomic analyses following CRZ2 genetic perturbation...
July 11, 2018: Cellular Microbiology
Naixin Zhang, Samiksha Prasad, Charles-Eugene Huyghues Despointes, Jeffrey Young, Peter E Kima
Miltefosine is an important drug for the treatment of leishmaniasis; however, its mechanism of action is still poorly understood. In these studies, we tested the hypothesis that like in cancer cells, miltefosine's efficacy in leishmaniasis is due to its inhibition of Akt activation in host cells. We show using pharmacologic agents that block Akt activation by different mechanisms and also using an inducible knockdown approach, that miltefosine loses its efficacy when its access to Akt1 is limited. Interestingly, limitation of Akt activation results in clearance of established Leishmania infections...
July 11, 2018: Cellular Microbiology
Athmanya Konegadde Eshwar, Nina Wolfrum, Roger Stephan, Séamus Fanning, Angelika Lehner
Bacteria belonging to the genus Cronobacter (C.) have been recognized as causative agents of life-threatening systemic infections primarily in premature and low-birth weight neonates. Validation of putative bacterial virulence components as well as host factors potentially involved in the response to infection have been hampered in the past by the availability of suitable neonatal animal models. In the current study the zebrafish embryo model was employed to study the interaction of the zinc metalloprotease Zpx present in C...
July 4, 2018: Cellular Microbiology
Roswitha Nast, Julia Staab, Thomas Meyer, Carsten G K Lüder
Toxoplasma gondii is an obligate intracellular parasite which infects up to 30% of humans world-wide. It can lead to severe diseases particularly in individuals with immature or defective immune responses. Control of T. gondii relies on the IFN-γ-induced signal transducer and activator of transcription (STAT)-1 pathway. T. gondii, however, largely inactivates STAT1-mediated gene transcription by TgIST (T. gondii inhibitor of STAT1-dependent transcription), a parasite effector protein binding to STAT1. Here, we have analyzed requirements of STAT1 to bind TgIST and characterized down-stream effects on STAT1 signaling...
July 2, 2018: Cellular Microbiology
Kurni Kurniyati, Jun Liu, Jing-Ren Zhang, Yunjiang Min, Chunhao Li
FlaG homolog has been found in several bacteria including spirochetes; however, its function is poorly characterized. In this report, we investigated the role of TDE1473, a putative FlaG, in the spirochete Treponema denticola, a keystone pathogen of periodontitis. TDE1473 resides in a large gene operon that is controlled by a σ70 -like promoter and encodes a putative FlaG protein of 123 amino acids. TDE1473 can be detected in the periplasmic flagella (PFs) of T. denticola, suggesting that it is a flagella-associated protein...
June 23, 2018: Cellular Microbiology
Quentin Bernard, Meghna Thakur, Alexis A Smith, Chrysoula Kitsou, Xiuli Yang, Utpal Pal
Borrelia burgdorferi is the causative agent of Lyme disease that persists in a complex enzootic life cycle, involving Ixodes ticks and vertebrate hosts. The microbe invades ticks and vertebrate hosts in spite of active immune surveillance and potent microbicidal responses, and establishes long-term infection utilizing mechanisms that are yet to be unraveled. The pathogen can cause multi-system disorders when transmitted to susceptible mammalian hosts, including in humans. In the past decades, several studies identified a limited number of B...
June 22, 2018: Cellular Microbiology
Gabriela Uribe, Romain Villéger, Philippe Bressollier, Rachel N Dillard, Daniel L Worthley, Timothy C Wang, Don W Powell, Maria C Urdaci, Irina V Pinchuk
Prostaglandin E2 (PGE2 ) plays a critical role in intestinal mucosal tolerance and barrier integrity. Cyclooxygenase-2 (COX-2)-dependent PGE2 production involves mobilization of arachidonic acid (AA). Lactobacillus rhamnosus GG (LbGG) is one of the most widely used probiotics reported to colonize the colonic mucosa. LbGG contributes to the protection of the small intestine against radiation injury through the repositioning of mucosal COX-2 expressing cells. However, it is unknown if LbGG modulates PGE2 production in the colonic mucosa under homeostasis and the major cellular elements involved in these processes...
June 19, 2018: Cellular Microbiology
Juliette Morlon-Guyot, Hiba El Hajj, Kevin Martin, Adrien Fois, Amandine Carrillo, Laurence Berry, Richard Burchmore, Markus Meissner, Maryse Lebrun, Wassim Daher
Apicomplexans use the endolysosomal system for the biogenesis of their secretory organelles, namely micronemes, rhoptries and dense granules. In Toxoplasma gondii, our previous in silico search identified the HOPS tethering but not the CORVET complex and demonstrated a role of Vps11 (a common component for both complexes) in its secretory organelles biogenesis. Herein, we performed Vps11-GFP-Trap pull-down assays and identified by proteomic analysis, not only the CORVET specific subunit Vps8, but also a BEACH domain-containing protein (BDCP) conserved in eukaryotes...
June 17, 2018: Cellular Microbiology
Ronald S Flannagan, David W Watson, Bas G Surewaard, Paul Kubes, David E Heinrichs
Staphylococcus lugdunensis is a commensal bacterium that can cause serious infection suggesting an ability to circumvent aspects of host immunity. We demonstrate here that macrophages fail to kill ingested S. lugdunensis and the bacteria persist for extended periods, without replicating, within mature LAMP-1-positive phagolysosomes. Phagocytosed S. lugdunensis also do not intoxicate host cells in contrast to S. aureus. Optimal survival of S. lugdunensis requires O-acetylated peptidoglycan since an oatA mutant, which is more sensitive to killing by lysozyme than WT, survived to a lesser extent in macrophages...
June 14, 2018: Cellular Microbiology
Lara-Antonia Beer, Helma Tatge, Nicole Reich, Michel Tenspolde, Alexandra Olling, Sebastian Goy, Klemens Rottner, Alexi Kirilov Alekov, Ralf Gerhard
Toxin A and Toxin B (TcdA/TcdB) are large glucosyltransferases produced by Clostridium difficile. TcdB but not TcdA induces reactive oxygen species-mediated early cell death (ECD) when applied at high concentrations. We found that nonglucosylated Rac1 is essential for induction of ECD since inhibition of Rac1 impedes this effect. ECD only occurs when TcdB is rapidly endocytosed. This was shown by generation of chimeras using the trunk of TcdB from a hypervirulent strain. TcdB from hypervirulent strain has been described to translocate from endosomes at higher pH values and thus, meaning faster than reference type TcdB...
June 14, 2018: Cellular Microbiology
Svetlana Glushakova, Josh R Beck, Matthias Garten, Brad L Busse, Armiyaw S Nasamu, Tatyana Tenkova-Heuser, John Heuser, Daniel E Goldberg, Joshua Zimmerberg
Because Plasmodium falciparum replicates inside of a parasitophorous vacuole (PV) within a human erythrocyte, parasite egress requires the rupture of two limiting membranes. Parasite Ca2+ , kinases, and proteases contribute to efficient egress; their coordination in space and time is not known. Here, the kinetics of parasite egress were linked to specific steps with specific compartment markers, using live-cell microscopy of parasites expressing PV-targeted fluorescent proteins, and specific egress inhibitors...
June 13, 2018: Cellular Microbiology
Bruno Guedes Aguiar, Prasad K Padmanabhan, Carole Dumas, Barbara Papadopoulou
Valosin-containing protein (VCP)/p97/Cdc48 is one of the best-characterised type II cytosolic AAA+ ATPases most known for their role in ubiquitin-dependent protein quality control. Here, we provide functional insights into the role of the Leishmania VCP/p97 homologue (LiVCP) in the parasite intracellular development. We demonstrate that although LiVCP is an essential gene, Leishmania infantum promastigotes can grow with less VCP. In contrast, growth of axenic and intracellular amastigotes is dramatically affected upon decreased LiVCP levels in heterozygous and temperature sensitive (ts) LiVCP mutants or the expression of dominant negative mutants known to specifically target the second conserved VCP ATPase domain, a major contributor of the VCP overall ATPase activity...
June 12, 2018: Cellular Microbiology
Kirsten C Boddy, Aggie Duan Gao, Dorothy Truong, Moshe S Kim, Carol D Froese, William S Trimble, John H Brumell
Actin nucleators and their binding partners play crucial roles during Salmonella invasion, but how these factors are dynamically coordinated remains unclear. Here, we show that septins, a conserved family of GTPases, play a role during the early stages of Salmonella invasion. We demonstrate that septins are rapidly recruited to sites of bacterial entry and contribute to the morphology of invasion ruffles. Expression of Septin 2, Septin 7 and Septin 9 is required for efficient bacterial invasion. We found that septins contribute to the recruitment of ROCK2 kinase during Salmonella invasion and the downstream activation of the actin nucleating protein FHOD1...
June 8, 2018: Cellular Microbiology
Zhendong Cai, Wenlong Du, Zheng Zhang, Luyu Guan, Qiuqiong Zeng, Yanfei Chai, Chuanchao Dai, Ling Lu
Copper (Cu) and zinc (Zn) are essential nutrients for both pathogens and hosts; however, their excess accumulation is toxic for all cells. The Aspergillus transcription factor AceA has been identified having function for Cu detoxification through up-regulation of the expression of the P-type ATPase, CrpA. Here, we demonstrate that Aspergillus fumigatus CrpA is involved in both Cu and Zn detoxification and a putative metallothionein AfCrdA plays a major function in Cu detoxification, and a putative transporter AfZrcA has a dominant role in Zn detoxification, but all three members are transcriptionally dependent on AfAceA...
May 29, 2018: Cellular Microbiology
Liesbeth Demuyser, Wouter Van Genechten, Hideaki Mizuno, Sonia Colombo, Patrick Van Dijck
The cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) pathway is central to signal transduction in many organisms. In pathogenic fungi such as Candida albicans, this signalling cascade has proven to be involved in several processes, such as virulence, indicating its potential importance in antifungal drug discovery. Candida glabrata is an upcoming pathogen of the same species, yet information regarding the role of cAMP-PKA signalling in virulence is largely lacking. To enable efficient monitoring of cAMP-PKA activity in this pathogen, we here present the usage of two FRET-based biosensors...
May 29, 2018: Cellular Microbiology
Liu Rui, Li Weiyi, Meng Yu, Zhou Hong, Yu Jiao, Ma Zhe, Fan Hongjie
Streptococcus suis serotype 2 (SS2) is a zoonotic agent that causes meningitis in humans and pigs. However, the mechanism whereby SS2 crosses the microvasculature endothelium of the brain is not understood. In this study, transposon (TnYLB-1) mutagenesis was used to identify virulence factors potentially associated with invasive ability in pathogenic SS2. A poorly invasive mutant was identified and was found to contain a TnYLB-1 insertion in the serine/threonine kinase (stk) gene. Transwell chambers containing hBMECs were used to model the blood-brain barrier (BBB)...
May 24, 2018: Cellular Microbiology
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