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Mechanisms of Action: Physiological EffectsAutophagy Induction by a Small Molecule Inhibits Salmonella Survival in Macrophages and MiceSalmonella enterica is a natural bacterial pathogen of humans and animals that causes systemic infection or gastroenteritis. During systemic infection, Salmonella generally resides within professional phagocytes, typically macrophages, whereas gastroenteritis is caused by infection of epithelial cells. We are only beginning to understand which host pathways...
SusceptibilityRegrowth of Mycobacterium tuberculosis Populations Exposed to Antibiotic Combinations Is Due to the Presence of Isoniazid and Not Bacterial Growth RateModulation of the growth rate in Mycobacterium tuberculosis is key to its survival in the host, particularly with regard to its adaptation during chronic infection, when the growth rate is very slow. The resulting physiological changes influence the way in which this pathogen interacts with the host and responds to antibiotics. Therefore, it is important that we...
Mechanisms of ResistanceComprehensive Genome Analysis of Carbapenem-Resistant Strains of Raoultella Species, an Emerging Multidrug-Resistant Bacterium in HospitalsWe report the characterization of six carbapenem-resistant Raoultella spp. (CRRS) in our hospital and a genomic analysis of 58 publicly available isolates. CRRS isolates are sporadically identified around the world, and different transposons carrying carbapenemases were the resistant mechanisms. Mobile genetic elements play an important role in acquiring antibiotic resistance genes from the hospital.
Clinical TherapeuticsSafety and Pharmacokinetics of a Four Monoclonal Antibody Combination against Botulinum C and D NeurotoxinsBotulism is caused by botulinum neurotoxin (BoNT), the most poisonous substance known. BoNTs are also classified as tier 1 biothreat agents due to their high potency and lethality. The existence of seven BoNT serotypes (A to G), which differ by 35% to 68% in amino acid sequences, necessitates the development of serotype-specific countermeasures.
Experimental TherapeuticsGC-072, a Novel Therapeutic Candidate for Oral Treatment of Melioidosis and Infections Caused by Select Biothreat PathogensBurkholderia pseudomallei, the etiological agent of melioidosis, is a Gram-negative bacterium with additional concern as a biothreat pathogen. The mortality rate from B. pseudomallei varies depending on the type of infection and extent of available health care; in the case of septicemia, left...
SusceptibilityDerepression of the smvA Efflux System Arises in Clinical Isolates of Proteus mirabilis and Reduces Susceptibility to Chlorhexidine and Other BiocidesProteus mirabilis is a common pathogen of the catheterized urinary tract and often described as intrinsically resistant to the biocide chlorhexidine (CHD). Here, we demonstrate that derepression of the smvA efflux system has occurred in clinical isolates of P. mirabilis and reduces...
SusceptibilityAntimicrobial Susceptibility and Molecular Characterization Using Whole-Genome Sequencing of Clostridioides difficile Collected in 82 Hospitals in Japan between 2014 and 2016We studied the antimicrobial susceptibility and molecular characteristics, using draft whole-genome sequencing, of Clostridioides (Clostridium) difficile strains before and after treatment in adults with...
Antiviral AgentsDoravirine Exposure and HIV-1 Suppression after Switching from an Efavirenz-Based Regimen to Doravirine-Lamivudine-Tenofovir Disoproxil FumarateDoravirine is a nonnucleoside reverse transcriptase inhibitor that has been approved for the treatment of HIV-1. In a phase 1 trial, doravirine exposure was transiently decreased when treatment was started immediately after the cessation of efavirenz treatment.
Mechanisms of Action: Physiological EffectsRexAB Is Essential for the Mutagenic Repair of Staphylococcus aureus DNA Damage Caused by Co-trimoxazoleCo-trimoxazole (SXT) is a combination therapeutic that consists of sulfamethoxazole and trimethoprim that is increasingly used to treat skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA). However, the use of SXT is limited to the treatment of low-burden, superficial...
Epidemiology and SurveillanceNo Evidence of Plasmodium falciparum k13 Artemisinin Resistance-Conferring Mutations over a 24-Year Analysis in Coastal Kenya but a Near Complete Reversion to Chloroquine-Sensitive ParasitesAntimalarial drug resistance is a substantial impediment to malaria control. The spread of resistance has been described using genetic markers, which are important epidemiological tools. We carried out a temporal analysis of changes in allele frequencies of 12 drug resistance markers over 2 decades of changing antimalarial drug policy in Kenya.