Bacterial Genotype, Carrier Risk Factors, and an Antimicrobial Stewardship Approach Relevant to Methicillin-resistant Staphylococcus aureus Prevalence in a Population of Macaques Housed in a Research Facility.

Methicillin-resistant Staphylococcus aureus (MRSA) remains a significant problem for human and animal health and can negatively affect the health status of macaques and other nonhuman primates (NHP) in research colonies. However, few publications provide guidance on the prevalence, genotype, or risk factors for macaques with MRSA and even fewer on how to effectively respond to MRSA once identified in a population. After having a clinical case of MRSA in a rhesus macaque, we sought to determine the MRSA carrier prevalence, risk factors, and genotypes of MRSA in a population of research NHPs. Over a 6-wk period in 2015, we collected nasal swabs from 298 NHPs. MRSA was isolated from 28% (n = 83). We then reviewed each macaque's medical record for a variety of variables including animal housing room, sex, age, number of antibiotic courses, number of surgical interventions, and SIV status. Analysis of these data suggests that MRSA carriage is associated with the room location, age of the animal, SIV status, and the number of antibiotic courses. We used multilocus sequence typing and spa typing on a subset of MRSA and MSSA isolates to determine whether the MRSA present in NHPs was comparable with common human strains. Two MRSA sequence types were predominant: ST188 and a novel MRSA genotype, neither of which is a common human isolate in the United States. We subsequently implemented antimicrobial stewardship practices (significantly reducing antimicrobial use) and then resampled the colony in 2018 and found that MRSA carriage had fallen to 9% (26/285). These data suggest that, as in humans, macaques may have a high carrier status of MRSA despite low clinically apparent disease. Implementing strategic antimicrobial stewardship practices resulted in a marked reduction in MRSA carriage in the NHP colony, highlighting the importance of limiting antimicrobial use when possible.

Cerebellar ataxia, seizures, premature death, and cardiac abnormalities in mice with targeted disruption of the Cacna2d2 gene.

CACNA2D2 is a putative tumor suppressor gene located in the human chromosome 3p21.3 region that shows frequent allelic imbalances in lung, breast, and other cancers. The alpha2delta-2 protein encoded by the gene is a regulatory subunit of voltage-dependent calcium channels and is expressed in brain, heart, and other tissues. Here we report that mice homozygous for targeted disruption of the Cacna2d2 gene exhibit growth retardation, reduced life span, ataxic gait with apoptosis of cerebellar granule cells followed by Purkinje cell depletion, enhanced susceptibility to seizures, and cardiac abnormalities. The Cacna2d2(tm1NCIF) null phenotype has much in common with that of Cacna1a mutants, such as cerebellar neuro-degeneration associated with ataxia, seizures, and premature death. A tendency to bradycardia and limited response of null mutants to isoflurane implicate alpha2delta-2 in sympathetic regulation of cardiac function. In summary, our findings provide genetic evidence that the alpha2delta-2 subunit serves in vivo as a component of P/Q-type calcium channels, is indispensable for the central nervous system function, and may be involved in hereditary cerebellar ataxias and epileptic disorders in humans.