Mostly Microbes and Infection - by David Ojcius

  Highlights • Bacterial serine proteases play a crucial role in the interaction between bacteria and their hosts, facilitating bacterial invasion and contributing to pathogenicity. Mycobacterium tuberculosis possesses multiple serine proteases; however, the mechanisms of action of these proteases remain incompletely understood. In this study, we characterized the role of a novel serine protease, Rv1815, by purifying it in Escherichia coli and creating a rv1815 deletion mutant in M. tuberculosis to investigate its function. Our research revealed that Rv1815 is located in the cytoplasm of macrophages, exhibits serine protease activity, and can be secreted extracellularly. Moreover, we found that rv1815 is essential for bacterial virulence, survival, metabolism, and antibiotic resistance, as demonstrated by proteomic analysis. Rv1815 also influences bacterial morphology, enhances bacterial growth in vitro, and promotes intracellular survival of M. tuberculosis in macrophages. Further...

  Highlights • Human cytomegalovirus RNA2.7 sequesters RNA-binding proteins to stabilize host mRNAs • RNA2.7 enforces G1-S arrest specifically in actively cycling cells • An adenosine-rich RNA2.7 region is required for cell-cycle arrest • RNA2.7-driven cell-cycle arrest promotes efficient HCMV replication

  Highlights • XAI–SERS platform enables accurate discrimination of  E. coli  pathotypes and  Shigella. • 1D-CNN model achieved 97.7% accuracy, surpassing traditional classifiers. • SHAP analysis identified key spectral features linked to molecular components. • Provides a precise, interpretable approach for bacterial diagnostics.

  Highlights • One-year multicenter survey of fosfomycin-resistant Enterobacterales in Czech Republic hospitals. • FosA3-producing  Proteus mirabilis  predominates. • FosA3-positive  P. mirabilis  ST185 forms a local clonal cluster while  E. coli  clones are heterogeneous. • Transporter defects (GlpT/UhpT) are widespread; most  fosA  strains carry ESBL genes. • Molecular surveillance is crucial to monitor and contain emerging fosfomycin resistance.

  Highlights • XDR  Klebsiella oxytoca  found in hospital wastewater with 59 resistance genes • Mega plasmid pKO611.1 carries 28 resistance genes, enabling multidrug resistance • Novel  tet (E) variant and AmpC β-lactamase confer tetracycline & β-lactam resistance • Plasmid pKO611.1 transfers efficiently to  Escherichia coli , spreading resistance • Plasmid recombination shows potential as resistance gene reservoir for dissemination

  Highlights • Aridity index, rather than degradation level, is the paramount driver shaping soil bacterial and fungal communities (explaining ∼43% and ∼30% of the variation, respectively). • The ecosystem harbors an exceptionally stable core microbiome, with 18,510 bacterial ASVs shared across aridity gradients. • Dry sub-humid (alternating wet-dry) conditions promote the most complex and stable microbial co-occurrence networks. • Community assembly of both bacteria and fungi is predominantly governed by stochastic processes (ecological drift). • Microbial functional profiling reveals nitrogen cycling as the dominant process, with distinct adaptations along the aridity gradient.

  Highlights • E. coli  isolates from healthy or diseased hosts exhibit distinct metabolic profiles • D-serine utilization is more prevalent in E. coli isolates from Crohn’s patients • The D-serine associated  dsdCXA  cluster enhances E. coli fitness in the gut

A new leadership team is now in place to help guide the future of research at the Arthur A. Dugoni School of Dentistry. Dr. David Ojcius, chair of the Department of Biomedical Sciences, was recently named to a new role as assistant dean for research. He will continue to serve as department chair in addition to his new duties. Ojcius brings a wide range of research, scholarship and leadership skills to this role.

Dean Prof. Dr. Zahid Yousaf of the University of Gujrat (UOG) embarked on a significant visit to the University of the Pacific, California, US, from May 20 to May 25. This visit was planned on the special invitation of Dr Qingwen Dong, Director graduate program and a leading academic from the department of communication. This visit not only facilitated fruitful discussions among academics from both countries but also laid the groundwork for a series of innovative collaborations between the two esteemed institutions. During this visit, Prof. Dr. Zahid Yousaf Engaged in dialogues with key stakeholders including President Christopher Callahan, Vice President Mary Lomax-Ghirarduzzi,  Associate Provost David Ojcius, Dean Lee Skinner, Director of International Scholars and Services, Patrick Wolak, Director Admissions among others. These meetings underscored a shared vision for enhancing academic cooperation and global engagement.

  Highlight • Blood SCFA concentrations are reduced in patients with depression, especially in clinically diagnosed patients. • SCFA supplementation may improve depressive-like behaviors in animal models. • SCFA deficiency may contribute to depression, supporting SCFAs as potential biomarkers and therapeutic targets.

University of the Pacific secured 62 grants from federal, state and county agencies totaling more than $36 million—one of the best years for government grants in school history. The dramatic increase in fiscal year 2023—double the amount awarded to Pacific in 2022—was largely driven by three of the university’s largest grants, which include $6 million for the School of Health Sciences to  expand the social work program , $5.6 million for Benerd College to  support mental health services in K-12 schools  and $5 million to McGeorge School of Law to  improve mental health services in California . This was the best year for grants at Pacific in 15 years. “This is a reflection of the exceptional work our faculty are doing to address pressing issues,” said David Ojcius, assistant provost for research and scholarship. “These grants will have a significant impact on the community.”   Read full article at: https://www.pacific.edu/pacific-newsroom/pacific-has-on...

  Highlights • MrkA is required for siderophore production, revealing an unexpected link between type 3 fimbriae and iron acquisition. • MrkA could mediates bacterial adhesion to bladder and intestinal epithelium, indicating a role in mucosal tropism. • MrkA maintains carbon homeostasis via the PTS and csrA, and its loss reprograms metabolism and attenuates virulence.

  Highlights • Grass types variably affect soil microbes and nutrient cycling gene abundance. • Carex breviculmis enhances soil C fixation, denitrification, and P activation. • Festuca arundinacea Schred promotes soil nitrogen fixation capacity. • Soil pH, AP and AN boost C/N/P/S-cycling genes.

  Highlights • Experimentally infected participants expel infectious influenza virus into the air • The magnitude of infectious expulsions varies widely by individual • Infectivity of expulsions correlates with viral loads and symptoms • Viral genetic diversity is maintained through the expulsion process

  Highlights • Type II CRISPR-Cas systems are highly prevalent in the human gut • Gut phages harbor diverse type II CRISPR inhibitors, including one for type II-B • Members of the GutAcr aca  family share similar structures but have diverse sequences • GutAcr aca  members inhibit bacterial immunity and regulate their own production

  Highlights • Colonocyte regionalization is microbiome-driven rather than stem cell intrinsic • Microbiome-derived nicotinic acid establishes proximal identity partly via PPARα • Microbiome-mediated proximal identity protects the colon from DSS-induced injury • In humans, proximal/ascending identity is lost in Crohn’s disease patients

  Highlights • Therapeutic Landscape Evolution : Current FDA-approved triple regimens feature sulbactam-durlobactam (SUL-DUR), the siderophore cephalosporin cefiderocol (FDC), and eravacycline. Zosurabalpin remains in Phase I evaluation, while  Acinetobacter baumannii  prophylactic vaccines are still undergoing preclinical development. • CRAB Treatment Paradigms : SUL-DUR combination therapy emerges as a promising first-line therapeutic candidate for critically ill patients with carbapenem-resistant  Acinetobacter baumannii  (CRAB) infections. FDC demonstrates pivotal potential in multidrug-resistant pathogen co-therapy frameworks through its innovative iron-transport mechanism. • Strategic Interventions : Dual-track approaches are imperative: 1) Accelerating CRAB-targeted drug development through priority review pathways, implementing adaptive clinical trial designs, and establishing dynamic risk management-based post-marketing surveillance systems; 2) Strength...

  Highlights • A single-cohort metaproteomics study of 1,967 fecal samples • Associations of gut metaproteome with 44 phenotypes • Microbial functional shifts associated with aging, metabolic diseases, and drugs • Megasphaera elsdenii  may contribute to blood glucose regulation

  Highlights • The flavor, nutritional, and probiotic properties of kefir are intrinsically linked to its distinctive microbial communities. • Both traditional and modern production methods of kefir exhibit certain inherent limitations. • Synthetic kefir microbial communities and kefir-like starter cultures have been proposed as innovative production approaches for kefir.

  Highlights • Proteome analysis supports  Chroococcidiopsis  sp. 029 for ISRU on Mars. • Perchlorates induce enzymatic and non-enzymatic antioxidants responses. • Perchlorates activate secondary metabolism and polyhydroxybutyrate biosynthesis. • Chroococcidiopsis  sp. 029 harbors methylotrophic potential for life support systems.

  Highlights • Comprehensive multi-omic analysis of the immune system and microbiome in healthy humans • Major axes of immune variation are driven by interferon response signatures • Specific immune cell states are coordinated with microbiome pathways and metabolites • Coordinated immune and microbiome features are stable within individuals over time

  Highlights • HDV triggers innate immune sensing but largely escapes interferon-mediated control • Nuclear replication limits HDV exposure to antiviral interferon-stimulated genes • HDV selectively impairs IFN-α signaling through USP18-mediated negative feedback • Interferon efficacy against HDV varies across viral genotypes and cell models • Understanding HDV-IFN interactions is key to optimizing future combination therapies

  Highlights • Whole-exome sequencing in severe rotavirus cases identified seven candidate SNPs, several linked to gastrointestinal cancer pathways. • Transcriptomic and epigenomic data supported functional involvement of top candidate genes and suggested roles in cancer progression. • Polygenic risk score analyses indicated reduced gastrointestinal cancer risk among individuals with severe early-life RV infection. • Evidence of recent positive selection in key SNPs supports a model of reverse antagonistic pleiotropy, suggesting early RV susceptibility may confer later-life cancer protection.

  Highlights • Deltaviruses hitchhike within helper virus virions, using them as viral Trojan Horses • The Trojan Horse model is mandatory for productive herpesvirus-deltavirus associations • This mode of propagation favors deltavirus infectivity • Trojan Horse model warrants screening for extra-hepatic deltavirus infections in humans