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Biology subjects

Graham, J. P.

Publications and source records attributed to Graham, J. P..

2 recordsLinked to original sources

Phylodynamics Uncovers the Transmission of Antibiotic-Resistant Escherichia coli between Canines and Humans in an Urban Environment

The role of canines in transmitting antibiotic resistant bacteria to humans in the urban environment is poorly understood. To elucidate this role, we utilized genomic sequencing and phylogenetics to characterize the burden and transmission dynamics of antibiotic resistant Escherichia coli (ABR-Ec) cultured from canine and human feces present on urban sidewalks in San Francisco, California. We collected a total of fifty-nine ABR-Ec from human (n=12) and canine (n=47) fecal samples from the Tenderloin and South of Market (SoMa) neighborhoods of San Francisco. We then analyzed phenotypic and genotypic antibiotic resistance (ABR) of the isolates, as well as clonal relationships based on cgMLST and single nucleotide polymorphisms (SNPs) of the core genomes. Using Bayesian inference, we reconstructed the transmission dynamics between humans and canines from multiple local outbreak clusters using the marginal structured coalescent approximation (MASCOT). Overall, we found human and canine samples to carry similar amounts and profiles of ABR genes. Our results provide evidence for multiple transmission events of ABR-Ec between humans and canines. In particular, we found one instance of likely transmission from canines to humans as well as an additional local outbreak cluster consisting of one canine and one human sample. Based on this analysis, it appears that canine feces act as an important reservoir of clinically relevant ABR-Ec within the urban environment. Our findings support that public health measures should continue to emphasize proper canine feces disposal practices, access to public toilets and sidewalk and street cleaning. Importance: Antibiotic resistance in E. coli is a growing public health concern with global attributable deaths projected to reach millions annually. Current research has focused heavily on clinical routes of antibiotic resistance transmission to design interventions while the role of alternative reservoirs such as domesticated animals remain less well understood. Our results suggest canines are part of the transmission network that disseminates high-risk multidrug resistance in E. coli within the urban San Francisco community. As such, this study highlights the need to consider canines, and potentially domesticated animals more broadly, when designing interventions to reduce the prevalence of antibiotic resistance in the community. Additionally, it showcases the utility of genomic epidemiology to reconstruct the pathways by which antimicrobial resistance spreads.

microbiology↗

Microbiome modulates immunotherapy response in cutaneous squamous cell carcinoma

The gut microbiome is increasingly recognized to alter cancer risk, progression, and response to treatments such as immunotherapy, especially in cutaneous melanoma. However, whether the microbiome influences immune checkpoint inhibitor (ICI) immunotherapy response to non-melanoma skin cancer has not yet been defined. As squamous cell carcinomas (SCC) are in closest proximity to the skin microbiome, we hypothesized that the skin microbiome, which regulates cutaneous immunity, might affect SCC-associated anti-PD1 immunotherapy treatment response. We used ultraviolet radiation to induce SCC in SKH1 hairless mice. We then treated the mice with broad-band antibiotics to deplete the microbiome, followed by colonization by candidate skin and gut bacteria or persistent antibiotic treatment, all in parallel with ICI treatment. We longitudinally monitored skin and gut microbiome dynamics by 16S rRNA gene sequencing, and tumor burden by periodic tumor measurements and histologic assessment. Our study revealed that antibiotics-induced abrogation of the microbiome reduced tumor burden, suggesting a functional role of the microbiome in non-melanoma skin cancer therapy response.

microbiology↗