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- Infectious Diseases
- 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.
Liver-Specific Transgenic Expression of Human NTCP In Rhesus Macaques Confers HBV Susceptibility on Primary Hepatocytes
Rust et al., PNAS. 2025.
https://pubmed.ncbi.nlm.nih.gov/39937851
This study establishes the first transgenic nonhuman primate model for hepatitis B virus (HBV). Male and female rhesus macaques were engineered to express the human HBV receptor, NTCP (hNTCP), specifically in the liver. Researchers used PiggyBac transposon technology to introduce a liver-specific NTCP transgene into embryos, which were then implanted into surrogate females. The resulting offspring expressed hNTCP in hepatocytes and demonstrated high susceptibility to HBV infection. This model overcomes the species-specific limitations of HBV research, providing a powerful tool for studying HBV biology and evaluating HBV treatments in a clinically relevant model system. Supported by ORIP (P51OD011092), NIDA, and NIAID.
Suppression of Viral Rebound by a Rev-Dependent Lentiviral Particle in SIV-Infected Rhesus Macaques
Hetrick et al., Gene Therapy. 2025.
https://pubmed.ncbi.nlm.nih.gov/39025983/
Viral reservoirs are a current major barrier that prevents an effective cure for patients with HIV. Antiretroviral therapy (ART) effectively suppresses viral replication, but ART cessation leads to viral rebound due to the presence of viral reservoirs. Researchers conducted in vivo testing of simian immunodeficiency virus (SIV) Rev-dependent vectors in SIVmac239-infected male and female Indian rhesus macaques, 3–6 years of age, to target viral reservoirs. Treatment with the SIV Rev-dependent vector reduced viral rebound and produced neutralizing antibodies following ART cessation. These results indicate the potential to self-control plasma viremia through a neutralizing antibody-based mechanism elicited by administration of Rev-dependent vectors. This research could guide future studies focused on investigating multiple vector injections and quantifying cell-mediated immune responses. Supported by ORIP (P51OD011104, P40OD028116), NIAID, and NIMH.
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.
Potent Broadly Neutralizing Antibodies Mediate Efficient Antibody-Dependent Phagocytosis of HIV-Infected Cells
Snow et al., PLOS Pathogens. 2024.
https://pubmed.ncbi.nlm.nih.gov/39466835
This study investigates the role of potent broadly neutralizing antibodies (bNAbs) in mediating antibody-dependent cellular phagocytosis (ADCP) of HIV-infected cells. Researchers developed a novel cell-based approach to assess the ADCP of HIV-infected cells expressing natural conformations of the viral envelope glycoprotein, which allows the virus to infect a host cell. The findings in this study demonstrate that bNAbs facilitate efficient ADCP, highlighting their potential in controlling HIV infection by promoting immune clearance of infected cells. This study provides valuable insights into antibody-mediated immune mechanisms and supports the development of antibody-based therapies and vaccines targeting HIV. Supported by ORIP (P51OD011106) and NIAID.
Phenotypic Characterization of Subtype A and Recombinant AC Transmitted/Founder Viruses From a Rwandan HIV-1 Heterosexual Transmission Cohort
Yue et al., Viruses. 2024.
https://pubmed.ncbi.nlm.nih.gov/39599821
HIV-1 is classified into several phylogenetic groups and subgroups, and to be effective, a vaccine would require broad activity across diverse viral strains. The most widespread group, M, is subdivided into several subgroups (A–D, F–H, J, K, and L). In a previous study, these researchers analyzed cohorts of people with recent or acute HIV infection in Rwanda. Subtype A was the dominant subtype, but a significant number of infections were caused by recombinants of subtypes A and C. This study assessed the characteristics of 16 infectious molecular clones (IMCs) of subtype A or AC recombinant viruses. Viral replication scores varied among the IMCs, and amino acid substitutions in the viral Gag gene were linked to higher replication activity. The sensitivity of different clones to broadly neutralizing antibodies also was assessed. This panel of well-characterized viral IMCs will support studies required to develop an effective HIV-1 vaccine. Supported by ORIP (P51OD011132) and NIAID.