Multidrug-resistant Shigella flexneri outbreak associated with a high-mortality spillover event into nonhuman primates.

Shigellosis is a gastrointestinal infection caused by species of Shigella. A large outbreak of Shigella flexneri serotype 2a occurred in Albuquerque, New Mexico (NM) between May 2021 and November 2023 that involved humans and nonhuman primates (NHP) from a local zoo. We analyzed the genomes of 202 New Mexico isolates as well as 15 closely related isolates from other states, and four from NHP. The outbreak was initially detected within men who have sex with men (MSM) but then predominantly affected people experiencing homelessness (PEH). Nearly 70% of cases were hospitalized and there was one human death. The outbreak extended into Albuquerque's BioPark Zoo, causing high morbidity and six deaths in NHPs. The NHP isolates were identical to those in the human outbreak. All isolates were multidrug-resistant, including towards fluoroquinolones, a first line treatment option which led to treatment failures in human and NHP populations. We demonstrate the transmission of this S. flexneri strain between humans and NHPs, causing fatalities in both populations. This study demonstrates the threat of antimicrobial resistant organisms to vulnerable human and primate populations and emphasizes the value of vigilant genomic surveillance within a One Health framework.

Characteristics of Persons With Secondary Detection of Severe Acute Respiratory Syndrome Coronavirus 2 ≥90 days After First Detection, New Mexico 2020.

The New Mexico Department of Health (NMDOH) conducted a matched case-control study to compare 315 persons (cases) with and 945 persons (controls) without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) secondary detection (ie, positive SARS-CoV-2 test ≥90 days after first detection as of December 10, 2020). Compared with controls, cases had greater odds of higher SARS-CoV-2 testing frequency (adjusted odds ratio [aOR] = 1.2), being female (aOR = 1.6), being non-Hispanic American Indian/Alaska Native (aOR = 2.3), having diabetes mellitus (aOR = 1.8), and residing and/or working in detention and/or correctional facilities (aOR = 4.7). Diagnostic tools evaluating infectiousness at secondary detection are urgently needed to inform infection control practices.

MEK/ERK signaling is a critical regulator of high-risk human papillomavirus oncogene expression revealing therapeutic targets for HPV-induced tumors.

Intracellular pathogens have evolved to utilize normal cellular processes to complete their replicative cycles. Pathogens that interface with proliferative cell signaling pathways risk infections that can lead to cancers, but the factors that influence malignant outcomes are incompletely understood. Human papillomaviruses (HPVs) predominantly cause benign hyperplasia in stratifying epithelial tissues. However, a subset of carcinogenic or "high-risk" HPV (hr-HPV) genotypes are etiologically linked to nearly 5% of all human cancers. Progression of hr-HPV-induced lesions to malignancies is characterized by increased expression of the E6 and E7 oncogenes and the oncogenic functions of these viral proteins have been widely studied. Yet, the mechanisms that regulate hr-HPV oncogene transcription and suppress their expression in benign lesions remain poorly understood. Here, we demonstrate that EGFR/MEK/ERK signaling, influenced by epithelial contact inhibition and tissue differentiation cues, regulates hr-HPV oncogene expression. Using monolayer cells, epithelial organotypic tissue models, and neoplastic tissue biopsy materials, we show that cell-extrinsic activation of ERK overrides cellular control to promote HPV oncogene expression and the neoplastic phenotype. Our data suggest that HPVs are adapted to use the EGFR/MEK/ERK signaling pathway to regulate their productive replicative cycles. Mechanistic studies show that EGFR/MEK/ERK signaling influences AP-1 transcription factor activity and AP-1 factor knockdown reduces oncogene transcription. Furthermore, pharmacological inhibitors of EGFR, MEK, and ERK signaling quash HPV oncogene expression and the neoplastic phenotype, revealing a potential clinical strategy to suppress uncontrolled cell proliferation, reduce oncogene expression and treat HPV neoplasia.