Randi L Foxall, Jillian Means, Ashley L Marcinkiewicz, Christopher Schillaci, Kristin DeRosia-Banick, Feng Xu, Jeffrey A Hall, Stephen H Jones, Vaughn S Cooper, Cheryl A Whistler
No abstract text is available yet for this article.
April 22, 2024: MBio
Adam J Roberts, Han Boon Ong, Simon Clare, Cordelia Brandt, Katherine Harcourt, Yegnasew Takele, Prakash Ghosh, Angela Toepp, Max Waugh, Daniel Matano, Anna Färnert, Emily Adams, Javier Moreno, Margaret Mbuchi, Christine Petersen, Dinesh Mondal, Pascale Kropf, Gavin J Wright
UNLABELLED: Visceral leishmaniasis is a deadly infectious disease and is one of the world's major neglected health problems. Because the symptoms of infection are similar to other endemic diseases, accurate diagnosis is crucial for appropriate treatment. Definitive diagnosis using splenic or bone marrow aspirates is highly invasive, and so, serological assays are preferred, including the direct agglutination test (DAT) or rK39 strip test. These tests, however, are either difficult to perform in the field (DAT) or lack specificity in some endemic regions (rK39), making the development of new tests a research priority...
April 19, 2024: MBio
Johannes Zimmermann, Agnes Piecyk, Michael Sieber, Carola Petersen, Julia Johnke, Lucas Moitinho-Silva, Sven Künzel, Lena Bluhm, Arne Traulsen, Christoph Kaleta, Hinrich Schulenburg
UNLABELLED: The microbiome expresses a variety of functions that influence host biology. The range of functions depends on the microbiome's composition, which can change during the host's lifetime due to neutral assembly processes, host-mediated selection, and environmental conditions. To date, the exact dynamics of microbiome assembly, the underlying determinants, and the effects on host-associated functions remain poorly understood. Here, we used the nematode Caenorhabditis elegans and a defined community of fully sequenced, naturally associated bacteria to study microbiome dynamics and functions across a major part of the worm's lifetime of hosts under controlled experimental conditions...
April 18, 2024: MBio
Lulu Yu, Vladimir Majerciak, Alexei Lobanov, Sameer Mirza, Vimla Band, Haibin Liu, Maggie Cam, Stephen H Hughes, Douglas R Lowy, Zhi-Ming Zheng
UNLABELLED: The integration of HPV DNA into human chromosomes plays a pivotal role in the onset of papillomavirus-related cancers. HPV DNA integration often occurs by linearizing the viral DNA in the E1/E2 region, resulting in the loss of a critical viral early polyadenylation signal (PAS), which is essential for the polyadenylation of the E6E7 bicistronic transcripts and for the expression of the viral E6 and E7 oncogenes. Here, we provide compelling evidence that, despite the presence of numerous integrated viral DNA copies, virus-host fusion transcripts originate from only a single integrated HPV DNA in HPV16 and HPV18 cervical cancers and cervical cancer-derived cell lines...
April 16, 2024: MBio
Libuše Váchová, Vítězslav Plocek, Jana Maršíková, Stanislava Rešetárová, Ladislava Hatáková, Zdena Palková
Gcn4p belongs to conserved AP-1 transcription factors involved in many cellular processes, including cell proliferation, stress response, and nutrient availability in yeast and mammals. AP-1 activities are regulated at different levels, such as translational activation or protein degradation, which increases the variability of regulation under different conditions. Gcn4p activity in unstructured yeast liquid cultures increases upon amino acid deficiency and is rapidly eliminated upon amino acid excess. Gcn2p kinase is the major described regulator of Gcn4p that enables GCN4 mRNA translation via the uORFs mechanism...
April 16, 2024: MBio
Brendyn M St Louis, Sydney M Quagliato, Yu-Ting Su, Gregory Dyson, Pei-Chung Lee
UNLABELLED: The Hippo kinases MST1 and MST2 initiate a highly conserved signaling cascade called the Hippo pathway that limits organ size and tumor formation in animals. Intriguingly, pathogens hijack this host pathway during infection, but the role of MST1/2 in innate immune cells against pathogens is unclear. In this report, we generated Mst1/2 knockout macrophages to investigate the regulatory activities of the Hippo kinases in immunity. Transcriptomic analyses identified differentially expressed genes (DEGs) regulated by MST1/2 that are enriched in biological pathways, such as systemic lupus erythematosus, tuberculosis, and apoptosis...
April 16, 2024: MBio
Aditya Banerjee, Chia-Yu Kang, Minjun An, B Ben Koff, Sham Sunder, Anuj Kumar, Livia M A Tenuta, Randy B Stockbridge
UNLABELLED: Microorganisms resist fluoride toxicity using fluoride export proteins from one of several different molecular families. Cariogenic species Streptococcus mutans and Candida albicans extrude intracellular fluoride using a CLCF F- /H+ antiporter and FEX fluoride channel, respectively, whereas oral commensal eubacteria, such as Streptococcus gordonii, export fluoride using a Fluc fluoride channel. In this work, we examine how genetic knockout of fluoride export impacts pathogen fitness in single-species and three-species dental biofilm models...
April 16, 2024: MBio
Yutian Feng, Danielle Arsenault, Artemis S Louyakis, Neta Altman-Price, Uri Gophna, R Thane Papke, Johann Peter Gogarten
In this study, we use pan-genomics to characterize the genomic variability of the widely dispersed halophilic archaeal species Halorubrum ezzemoulense (Hez ). We include a multi-regional sampling of newly sequenced, high-quality draft genomes. The pan-genome graph of the species reveals 50 genomic islands that represent rare accessory genetic capabilities available to members. Most notably, we observe rearrangements that have led to the insertion/recombination/replacement of mutually exclusive genomic islands in equivalent genome positions ("homeocassettes")...
April 15, 2024: MBio
Julia R Palmucci, Blake E Sells, Charles D Giamberardino, Dena L Toffaletti, Baodi Dai, Yohannes G Asfaw, Laura G Dubois, Zhong Li, Barbara Theriot, Wiley A Schell, William Hope, Jennifer L Tenor, John R Perfect
Invasive fungal infections are a significant public health concern, with mortality rates ranging from 20% to 85% despite current treatments. Therefore, we examined whether a ketogenic diet could serve as a successful treatment intervention in murine models of Cryptococcus neoformans and Candida albicans infection in combination with fluconazole-a low-cost, readily available antifungal therapy. The ketogenic diet is a high-fat, low-carbohydrate diet that promotes fatty acid oxidation as an alternative to glycolysis through the production of ketone bodies...
April 15, 2024: MBio
Juan G Ripoll, Sidna M Tulledge-Scheitel, Anthony A Stephenson, Shane Ford, Marsha L Pike, Ellen K Gorman, Sara N Hanson, Justin E Juskewitch, Alex J Miller, Solomiia Zaremba, Erik A Ovrom, Raymund R Razonable, Ravindra Ganesh, Ryan T Hurt, Erin N Fischer, Amber N Derr, Michele R Eberle, Jennifer J Larsen, Christina M Carney, Elitza S Theel, Sameer A Parikh, Neil E Kay, Michael J Joyner, Jonathon W Senefeld
Although severe coronavirus disease 2019 (COVID-19) and hospitalization associated with COVID-19 are generally preventable among healthy vaccine recipients, patients with immunosuppression have poor immunogenic responses to COVID-19 vaccines and remain at high risk of infection with SARS-CoV-2 and hospitalization. In addition, monoclonal antibody therapy is limited by the emergence of novel SARS-CoV-2 variants that have serially escaped neutralization. In this context, there is interest in understanding the clinical benefit associated with COVID-19 convalescent plasma collected from persons who have been both naturally infected with SARS-CoV-2 and vaccinated against SARS-CoV-2 ("vax-plasma")...
April 11, 2024: MBio
Pei Li, Yajie Liu, Julia N Faraone, Cheng Chih Hsu, Michelle Chamblee, Yi-Min Zheng, Claire Carlin, Joseph S Bednash, Jeffrey C Horowitz, Rama K Mallampalli, Linda J Saif, Eugene M Oltz, Daniel Jones, Jianrong Li, Richard J Gumina, Shan-Lu Liu
UNLABELLED: The rapid evolution of SARS-CoV-2 variants presents a constant challenge to the global vaccination effort. In this study, we conducted a comprehensive investigation into two newly emerged variants, BA.2.87.1 and JN.1, focusing on their neutralization resistance, infectivity, antigenicity, cell-cell fusion, and spike processing. Neutralizing antibody (nAb) titers were assessed in diverse cohorts, including individuals who received a bivalent mRNA vaccine booster, patients infected during the BA...
April 9, 2024: MBio
Xiangyu Zhang, Shun Li, Mengzhou Xue
A recent study published in mBio by Cao et al. revealed the crucial roles of bacteria in benefitting SARS-CoV-2 mutations (B. Cao, X. Wang, W. Yin, Z. Gao, and B. Xia, mBio e3187-23, 2024, Understanding the underlying mechanisms driving the evolution of SARS-CoV-2 is crucial for predicting the future trajectory of the COVID-19 pandemic and developing preventive and treatment strategies. This study provides important insights into the rapid and complex evolution of viruses facilitated by bacterial-virus interactions...
April 9, 2024: MBio
Yue Zhou, Gregory A Phelps, Mikayla M Mangrum, Jemma McLeish, Elise K Phillips, Jinchao Lou, Christelle F Ancajas, Jeffrey M Rybak, Peter M Oelkers, Richard E Lee, Michael D Best, Todd B Reynolds
UNLABELLED: Systemic infections by Candida spp. are associated with high mortality rates, partly due to limitations in current antifungals, highlighting the need for novel drugs and drug targets. The fungal phosphatidylserine synthase, Cho1, from Candida albicans is a logical antifungal drug target due to its importance in virulence, absence in the host, and conservation among fungal pathogens. Inhibitors of Cho1 could serve as lead compounds for drug development, so we developed a target-based screen for inhibitors of purified Cho1...
April 9, 2024: MBio
Najing Cao, Yanxing Cai, Xin Huang, Hanxiao Jiang, Ziqi Huang, Lixiao Xing, Lu Lu, Shibo Jiang, Wei Xu
Outbreaks of acute respiratory viral diseases, such as influenza and COVID-19 caused by influenza A virus (IAV) and SARS-CoV-2, pose a serious threat to global public health, economic security, and social stability. This calls for the development of broad-spectrum antivirals to prevent or treat infection or co-infection of IAV and SARS-CoV-2. Hemagglutinin (HA) on IAV and spike (S) protein on SARS-CoV-2, which contain various types of glycans, play crucial roles in mediating viral entry into host cells. Therefore, they are key targets for the development of carbohydrate-binding protein-based antivirals...
April 9, 2024: MBio
Debra E Bessen, Bernard W Beall, Andrew Hayes, Weihua Huang, Jeanne M DiChiara, Srinivasan Velusamy, Hervé Tettelin, Keith A Jolley, John T Fallon, Sopio Chochua, Mosaed S A Alobaidallah, Charlie Higgs, Timothy C Barnett, John T Steemson, Thomas Proft, Mark R Davies
Among genes present in all group A streptococci (GAS), those encoding M-fibril and T-pilus proteins display the highest levels of sequence diversity, giving rise to the two primary serological typing schemes historically used to define strain. A new genotyping scheme for the pilin adhesin and backbone genes is developed and, when combined with emm typing, provides an account of the global GAS strain population. Cluster analysis based on nucleotide sequence similarity assigns most T-serotypes to discrete pilin backbone sequence clusters, yet the established T-types correspond to only half the clusters...
April 9, 2024: MBio
Shantanu Guha, Shane A Cristy, Giuseppe Buda De Cesare, Melissa R Cruz, Michael C Lorenz, Danielle A Garsin
UNLABELLED: Fungal resistance to commonly used medicines is a growing public health threat, and there is a dire need to develop new classes of antifungals. We previously described a peptide produced by Enterococcus faecalis , EntV, that restricts Candida albicans to a benign form rather than having direct fungicidal activity. Moreover, we showed that one 12-amino acid (aa) alpha helix of this peptide retained full activity, with partial activity down to the 10aa alpha helix. Using these peptides as a starting point, the current investigation sought to identify the critical features necessary for antifungal activity and to screen for new variants with enhanced activity using both biofilm and C...
April 9, 2024: MBio
Amaris J Cardenas, Keena S Thomas, Mary W Broden, Noel J Ferraro, Marcos M Pires, Constance M John, Gary A Jarvis, Alison K Criss
UNLABELLED: Gonorrhea, caused by the bacterium Neisseria gonorrhoeae (Gc), is characterized by neutrophilic influx to infection sites. Gc has developed mechanisms to resist killing by neutrophils that include modifications to its surface lipooligosaccharide (LOS). One such LOS modification is sialylation: Gc sialylates its terminal LOS sugars with cytidine-5'-monophosphate- N -acetylneuraminic acid, which is scavenged from the host using LOS sialyltransferase (Lst) since Gc cannot make its sialic acid...
April 9, 2024: MBio
Leopoldo F M Machado, Jorge E Galán
UNLABELLED: Salmonella enterica serovar Typhi and Paratyphi A are the cause of typhoid and paratyphoid fever in humans, which are systemic life-threatening illnesses. Both serovars are exclusively adapted to the human host, where they can cause life-long persistent infection. A distinct feature of these serovars is the presence of a relatively high number of degraded coding sequences coding for metabolic pathways, most likely a consequence of their adaptation to a single host. As a result of convergent evolution, these serovars shared many of the degraded coding sequences although often affecting different genes in the same metabolic pathway...
April 4, 2024: MBio
Jiejie Shen, Wenping Wu, Kangle Wang, Jingyi Wu, Bing Liu, Chunyang Li, Zijun Gong, Xin Hong, Han Fang, Xingwei Zhang, Xiaoling Xu
Acetyl-CoA carboxylases (ACCs) convert acetyl-CoA to malonyl-CoA, a key step in fatty acid biosynthesis and autotrophic carbon fixation pathways. Three functionally distinct components, biotin carboxylase (BC), biotin carboxyl carrier protein (BCCP), and carboxyltransferase (CT), are either separated or partially fused in different combinations, forming heteromeric ACCs. However, an ACC with fused BC-BCCP and separate CT has not been identified, leaving its catalytic mechanism unclear. Here, we identify two BC isoforms (BC1 and BC2) from Chloroflexus aurantiacus , a filamentous anoxygenic phototroph that employs 3-hydroxypropionate (3-HP) bi-cycle rather than Calvin cycle for autotrophic carbon fixation...
April 4, 2024: MBio
Vivian C Salgueiro, Charlotte Passemar, Lucía Vázquez-Iniesta, Laura Lerma, Andrés Floto, Rafael Prados-Rosales
Since the discovery of extracellular vesicles (EVs) in mycobacterial species 15 years back, we have learned that this phenomenon is conserved in the Mycobacterium genus and has critical roles in bacterial physiology and host-pathogen interactions. Mycobacterium tuberculosis ( Mtb ), the tuberculosis (TB) causative agent, produces EVs both in vitro and in vivo including a diverse set of biomolecules with demonstrated immunomodulatory effects. Moreover, Mtb EVs (MEVs) have been shown to possess vaccine properties and carry biomarkers with diagnostic capacity...
April 3, 2024: MBio
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