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- Infectious Diseases
- T32
- Genetics
Whole-Genome Sequences of Six Borrelia recurrentis Strains Obtained via PacBio Sequencing
Gaber et al., Microbiology Resource Announcements. 2025.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11895452
The spirochetal bacterium Borrelia recurrentis causes louse-borne relapsing fever (LBRF), which leads to significant morbidity and mortality in several African countries. Previous sequencing studies of B. recurrentis demonstrated discrepancies and did not accurately define the antigenic variation system. In this study, researchers used long-read PacBio technology to conduct whole-genome sequencing of six B. recurrentis strains that had been isolated from LBRF patients earlier. The resulting sequences of each genome included one linear chromosome and five linear plasmids, whose average size was 1,284,895 bp, with the mean GC content being 27.5%. Supported by ORIP (T32OD011083) and NIAID.
Antimicrobial Resistance of Vibrio spp. from the Coastal California System: Discordance Between Genotypic and Phenotypic Patterns
Sebastian et al., Applied and Environmental Microbiology. 2025.
https://pubmed.ncbi.nlm.nih.gov/39898660
Vibriosis, infection with non-cholera Vibrio spp., is the most common seafood-borne illness globally, with major impacts on public health, food security, and wildlife health. Potential treatments for antimicrobial-resistant Vibrio spp. in humans, aquaculture, and marine wildlife are complicated by current diagnostic challenges regarding bacterial species identification and interpretation of antimicrobial resistance patterns. Researchers sequenced 489 Vibrio spp. isolates, and antibiotic susceptibility testing was performed to compare the presence of resistance genes with phenotypes. Results determined that the presence of ß-lactamase genes alone in sea otter isolates does not necessarily correlate with an ampicillin-resistant phenotype, likely due to deleterious amino acid substitutions in certain blaCARB alleles. Unexpected detection of previously misidentified Vibrio diabolicus in sea otters suggests that a broader taxonomic group of Vibrio infect sea otters than previously described. Continued monitoring of Vibrio spp. phenotypes and genotypes in sea otters is warranted to observe biologically relevant changes in antimicrobial resistance. Supported by ORIP (T32OD011147).
Quorum Sensing LuxR Proteins VjbR and BabR Jointly Regulate Brucella abortus Survival During Infection
Caudill et al., Journal of Bacteriology. 2025.
https://pubmed.ncbi.nlm.nih.gov/40013834
Brucella abortus is a zoonotic bacterial pathogen that causes brucellosis, a persistent chronic infection that is globally endemic. B. abortus uses quorum sensing to escape immune clearance attempts, regulate virulence, and cause persistent infection within hosts. B. abortus quorum sensing system comprises two LuxR proteins, VjbR and BabR, as well as two signals, dodecanoyl (C12 AHL) and 3-oxododecanoyl (3-OXO-C12 AHL) homoserine lactone. Using chronic infection 6- to 7-week-old C57Bl/6 and BALB/c male and female mouse models, researchers found that the ΔvjbRΔbabR double-deletion strain was attenuated compared with single mutants. These results demonstrate that both quorum sensing proteins, VjbR and BabR, coordinate to maintain survival. This study helps further characterize the Brucella quorum sensing systems and indicates that further attention should be given to the joint interactions between VjbR and BabR in controlling virulence. Supported by ORIP (T32OD028239) and NIAID.
Prostatic Escherichia coli Infection Drives CCR2-Dependent Recruitment of Fibrocytes and Collagen Production
Scharpf et al., Disease Models & Mechanisms. 2025.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11789281
In men, lower urinary tract dysfunction (LUTD) is commonly linked to prostatic collagen accumulation through inflammation-mediated mechanisms. Researchers used 8- to 10-week-old male reporter mice, exposed to either sterile phosphate buffered saline (PBS) or Escherichia coli, to identify that circulating Lyz2+S100a4+Gli1+ myeloid-derived cells are recruited to the prostate to drive inflammation and collagen synthesis. Researchers also used 8- to 10-week-old male Ccr2‑/ - null and Ccr2+/- control mice, exposed to either sterile PBS or E. coli, to determine if Ccr2 is necessary for the fibrotic response to prostatic uropathogen infection. Results demonstrated that CCR2+ cells mediate the collagen abundance and fibrotic response to prostate inflammation. This study elucidates the cell types underlying prostate fibrosis and can be utilized to develop targeted therapies. Supported by ORIP (T32OD010957), NCI, NIDDK, and NIEHS.
A Murine Model of Trypanosoma brucei-Induced Myocarditis and Cardiac Dysfunction
Crilly et al., Microbiology Spectrum. 2025.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11792545
Trypanosoma brucei is a protozoan parasite that causes human and animal African trypanosomiases, HAT and AAT, respectively. Cardiac symptoms are commonly reported in HAT patients, and intracardiac parasites with accompanying myocarditis have been observed in both natural hosts and animal models for T. brucei infection. A clinically relevant, reproducible murine model for T. brucei–associated cardiomyopathy is currently unavailable. The researchers developed a 7- to 10-week-old C57Bl/6J male and female mouse model for T. brucei infection that demonstrates myocarditis, elevated serum levels of NT-proBNP, and electrocardiographic abnormalities, recapitulating the clinical features of infection. The results demonstrate the importance of interstitial space in T. brucei colonization and provide a relevant, reproducible murine model to investigate the pathogenesis and potential therapeutics of T. brucei-mediated heart damage. Supported by ORIP (T32OD011089, S10OD026859), NCI, and NIA.
A Switch from Glial to Neuronal Gene Expression Alterations in the Spinal Cord of SIV-Infected Macaques on Antiretroviral Therapy
Mulka et al., Journal of Neuroimmune Pharmacology. 2024.
https://pubmed.ncbi.nlm.nih.gov/38862787/
Up to one-third of patients with HIV experience HIV-associated peripheral neuropathy, affecting sensory pathways in the spinal cord. Spinal cord sampling is limited in people with HIV. Researchers examined gene expression alterations in the spinal cords of simian immunodeficiency virus (SIV)-infected male pigtail macaques with and without antiretroviral therapy (ART), using RNA sequencing at key time points throughout infection. Results indicate a shift from glial cell-associated pathways to neuronal pathways in SIV-infected animals receiving ART. These findings suggest that neurons, rather than glia, are predominantly involved in ART-related neurotoxicity and offer new insights into therapeutic strategies for maintaining synaptic homeostasis. Supported by ORIP (U42OD013117, T32OD011089) and NINDS.
Temperature-Dependent Alterations in the Proteome of the Emergent Fish Pathogen Edwardsiella piscicida
Jacobsen et al., Journal of Fish Diseases. 2024.
https://pubmed.ncbi.nlm.nih.gov/39304982
Reported outbreaks of Edwardsiella piscicida, a bacterial pathogen among cultured and wild fish, have been steadily increasing over the past decade in tandem with climate change–mediated increases in water temperatures. The capacity for this increasingly prevalent fish pathogen to infect and cause disease in mammals is important to understand. Researchers examined the role of temperature on the virulence of E. piscicida to understand its pathogenesis in the context of climate warming trends and better understand its zoonotic potential. Findings revealed downregulation of virulence-related proteins, such as flagellar and Type VI secretion system proteins, at colder temperatures. These findings highlight the potential environmental factors influencing the pathogen’s threat to aquaculture and public health. Supported by ORIP (S10OD026918, T32OD011147).
Innate Lymphoid Cells and Interferons Limit Neurologic and Articular Complications of Brucellosis
Moley et al., American Journal of Pathology. 2023.
https://www.sciencedirect.com/science/article/pii/S0002944023001980?via%3Dihub=
Brucellosis is a globally significant zoonotic disease. The current study investigated the role of innate lymphoid cells (ILCs) in the pathogenesis of focal brucellosis caused by Brucella melitensis. Following pulmonary infection with B. melitensis, mice lacking adaptive immune cells and ILCs developed arthritis, neurologic complications, and meningitis. Transcriptional analysis of Brucella-infected brains revealed marked upregulation of genes associated with inflammation and interferon responses. Collectively, these findings indicate that ILCs and interferons play an important role in prevention of focal complications during Brucella infection and that mice with deficiencies in ILCs or interferons can be used to study pathogenesis of neurobrucellosis. Supported by ORIP (T32OD011126) and NIAID.
The Incompetence of Mosquitoes—Can Zika Virus Be Adapted to Infect Culex tarsalis Cells?
Gallichotte et al., mSphere . 2023.
Zika virus (ZIKV) is transmitted between humans by Aedes aegypti mosquitoes. However, the 2015 to 2017 outbreak raised questions regarding the role of Culex species mosquitoes in transmission. Investigators attempted to adapt ZIKV to C. tarsalis by serially passaging the virus on cocultured A. aegypti and C. tarsalis cells to identify viral determinants of species specificity. Next-generation sequencing of cocultured virus passages revealed variants of interest that were engineered into nine recombinant viruses. None of these viruses showed increased infection of Culex cells or mosquitoes. Thus, although ZIKV might infect Culex mosquitoes occasionally, Aedes mosquitoes likely drive transmission and human risk. Supported by ORIP (T32OD010437) and NIAID.