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Benjamin P. Howden

Publications and source records attributed to Benjamin P. Howden.

2 recordsLinked to original sources
bioRxiv2016

Refutation: Spontaneous secondary mutations confound analysis of the essential two component system WalKR in Staphylococcus aureus

Ji et al.,1 recently detailed the structure of the extracytoplasmic Per-Arnt-Sim (PAS) domain of WalK (WalKEC-PAS), the sensor kinase of the essential two-component system WalKR in Staphylococcus aureus. The authors made two independent walK mutants in S. aureus, each with a single amino acid alteration in WalKEC-PAS. They postulated from comparative structural analysis and primary sequence comparisons that these residues might be important for extra cellular signal transduction. We have also been exploring the function of WalKR and were surprised by the striking phenotypic impact of a single amino acid substitutions in the WalK sensor, which were contrary to our own unpublished observations.\n\nThe authors subjected their WalKEC-PAS mutants (WalKD119A and WalKVl49A) to a series of phenotypic screens to probe the function of this domain. Compared to the parental methicillin sensiti ...

Microbiology↗
bioRxiv2016

Increasing tolerance of hospital Enterococcus faecium to hand-rub alcohols

Alcohol-based hand rubs are international pillars of hospital infection control, restricting transmission of pathogens such as Staphylococcus aureus. Despite this success, health care infections caused by Enterococcus faecium (Efm) - another multidrug resistant pathogen - are increasing. We tested alcohol tolerance of 139 hospital Efm isolates, obtained between 1997 and 2015 and found Efm post-2010 were 10-fold more tolerant to alcohol killing than older isolates. Using a mouse infection control model, we then showed that alcohol tolerant Efm resisted standard 70% isopropanol surface disinfection and led to gastrointestinal colonization significantly more often than alcohol sensitive Efm. We next looked for bacterial genomic signatures of adaptation. Tolerant Efm have independently accumulated mutations modifying genes involved in carbohydrate uptake and metabolism. Mutagenesis confirmed their roles in isopropanol tolerance. These findings suggest bacterial adaptation and complicate infection control recommendations. Additional policies and procedures to prevent Efm spread are required.

Microbiology↗