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Biology subjects

Goldberg, T. L.

Publications and source records attributed to Goldberg, T. L..

5 recordsLinked to original sources

Antimicrobial use contributes to resistance gene enrichment across cattle groups on commercial dairy farms

Antimicrobial use (AMU) in agricultural systems is frequently linked to antimicrobial resistance (AMR). Yet, the scale at which AMU reshapes host-associated resistomes remains unclear. This gap arises, in part, from the scarcity of farm-level AMU data from commercial production systems. Here, we combine detailed AMU records from commercial dairy farms with metagenomic analyses of bovine fecal resistomes from calves, lactating cows, sick cows, and cull cows. At a broad level, resistome profiles were similar regardless of farm AMU. Resistance associated with historically common antibiotics, such as tetracyclines, was frequent on low- and high-AMU farms, indicating that some resistance classes are ubiquitous in dairy systems regardless of current AMU. In contrast, resistance to other drug classes varied systematically with AMU. Higher AMU was associated with increased resistance to aminoglycosides, {beta}-lactams, and macrolides, drug classes that are critical for treating mastitis and bovine respiratory disease. Resistance gene richness and diversity were highest in calves, underscoring the importance of accounting for host traits alongside AMU when evaluating resistance patterns. Together, these findings underscore the need for detailed, farm-level AMU data to understand how management practices shape AMR and to inform strategies for sustaining the effectiveness of existing antimicrobials in agricultural and public-health contexts.

genomics↗

A previously uncharacterized gene in SARS-CoV-2 illuminates the functional dynamics and evolutionary origins of the COVID-19 pandemic

Understanding the emergence of novel viruses requires an accurate and comprehensive annotation of their genomes. Overlapping genes (OLGs) are common in viruses and have been associated with pandemics, but are still widely overlooked. We identify and characterize ORF3d, a novel OLG in SARS-CoV-2 that is also present in Guangxi pangolin-CoVs but not other closely related pangolin-CoVs or bat-CoVs. We then document evidence of ORF3d translation, characterize its protein sequence, and conduct an evolutionary analysis at three levels: between taxa (21 members of Severe acute respiratory syndrome-related coronavirus), between human hosts (3978 SARS-CoV-2 consensus sequences), and within human hosts (401 deeply sequenced SARS-CoV-2 samples). ORF3d has been independently identified and shown to elicit a strong antibody response in COVID-19 patients. However, it has been misclassified as the unrelated gene ORF3b, leading to confusion. Our results liken ORF3d to other accessory genes in emerging viruses and highlight the importance of OLGs.

evolutionary biology↗

Genomic and transcriptomic evidence for descent from Plasmodium and loss of blood schizogony in Hepatocystis parasites from naturally infected red colobus monkeys

Hepatocystis is a genus of single-celled parasites infecting monkeys, bats and squirrels. Although thought to descend from malaria parasites (Plasmodium spp.), Hepatocystis spp. are thought not to undergo replication in the blood - the part of the Plasmodium life cycle which causes the symptoms of malaria. Furthermore, Hepatocystis is transmitted by midges, not mosquitoes. Comparative genomics of Hepatocystis and Plasmodium species therefore presents an opportunity to better understand some of the most important aspects of malaria parasite biology. We were able to generate a draft genome for Hepatocystis using DNA sequencing reads from the blood of a naturally infected red colobus monkey. We provide robust phylogenetic support for Hepatocystis as a sister group to Plasmodium parasites infecting rodents. We show transcriptomic support for a lack of replication in the blood and genomic support for a complete loss of a family of genes involved in red blood cell invasion. Our analyses highlight the rapid evolution of genes involved in parasite vector stages, revealing genes that may be critical for interactions between malaria parasites and mosquitoes.

genomics↗

The evolution of a super-swarm of foot-and-mouth disease virus in cattle

Foot-and-mouth disease (FMD) is a highly contagious viral disease that severely impacts global food security and is one of the greatest constraints on international trade of animal products. Extensive viral population diversity and rapid, continuous mutation of circulating FMD viruses (FMDVs) pose significant obstacles to the control and ultimate eradication of this important transboundary pathogen. The current study investigated mechanisms contributing to within-host evolution of FMDV in a natural host species (cattle). Specifically, vaccinated and non-vaccinated cattle were infected with FMDV under controlled, experimental conditions and subsequently sampled for up to 35 days to monitor viral genomic changes as related to phases of disease and experimental cohorts. Consensus-level genomic changes across the entire FMDV coding region were characterized through three previously defined stages of infection: early, transitional, and persistent. The overall conclusion was that viral evolution occurred via a combination of two mechanisms: emergence of full-genomic minority haplotypes from within the inoculum super-swarm, and concurrent continuous point mutations. Phylogenetic analysis indicated that individuals were infected with multiple distinct haplogroups that were pre-existent within the ancestral inoculum used to infect all animals. Multiple shifts of dominant viral haplotype took place during the early and transitional phases of infection, whereas few shifts occurred during persistent infection. These insights into FMDV population dynamics have important implications for virus sampling methodology and molecular epidemiology.

microbiology↗

Genome-wide patterns of gene expression in a wild primate indicate species-specific mechanisms associated with tolerance to natural simian immunodeficiency virus infection

Over 40 species of nonhuman primates host simian immunodeficiency viruses (SIVs). In natural hosts, infection is generally assumed to be nonpathogenic due to a long coevolutionary history between host and virus, although pathogenicity is difficult to study in wild nonhuman primates. We used whole-blood RNA-seq and SIV prevalence from 29 wild Ugandan red colobus (Piliocolobus tephrosceles) to assess the effects of SIV infection on host gene expression in wild, naturally SIV-infected primates. We found no evidence for chronic immune activation in infected individuals, suggesting that SIV is not immunocompromising in this species, in contrast to HIV in humans. Notably, an immunosuppressive gene, CD101, was upregulated in infected individuals. This gene has not been previously described in the context of nonpathogenic SIV infection. This expands the known variation associated with SIV infection in natural hosts, and may suggest a novel mechanism for tolerance of SIV infection in the Ugandan red colobus.

genomics↗