A Genetic Locus in Elizabethkingia anophelis Associated with Elevated Vancomycin Resistance and Multiple Antibiotic Reduced Susceptibility

• Published in: Antibiotics (Basel) Vol. 13; no. 1; p. 61
• Main Authors: Johnson, William L, Gupta, Sushim Kumar, Maharjan, Suman, Morgenstein, Randy M, Nicholson, Ainsley C, McQuiston, John R, Gustafson, John E
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.01.2024
• Subjects: Amino acids; Antibiotic resistance; Antibiotics; Antimicrobial agents; Antimicrobial resistance; Binding sites; Cell walls; Drug resistance; elevated vancomycin resistance; Elizabethkingia; Elizabethkingia anophelis; Epidemics; Genomes; Infections; Lysis; Membrane permeability; Membrane proteins; Membranes; Mortality; multiple antibiotic resistance; Mutants; Mutation; Organisms; padR family transcriptional regulators; Pathogens; Permeability; Phage shock protein; Proteins; Single-nucleotide polymorphism; Vancomycin; vancomycin selection; vancomycin selection; Elizabethkingia anophelis; elevated vancomycin resistance; multiple antibiotic resistance; padR family transcriptional regulators
• ISSN: 2079-6382; 2079-6382
• DOI: 10.3390/antibiotics13010061

The Gram-negative express multiple antibiotic resistance and cause severe opportunistic infections. Vancomycin is commonly used to treat Gram-positive infections and has also been used to treat infections, even though Gram-negative organisms possess a vancomycin permeability barrier. appeared relatively vancomycin-susceptible and challenge with this drug led to morphological changes indicating cell lysis. In stark contrast, vancomycin growth challenge revealed that populations refractory to vancomycin emerged. In addition, vancomycin-selected mutants arose at high frequencies and demonstrated elevated vancomycin resistance and reduced susceptibility to other antimicrobials. All mutants possessed a SNP in a gene ( = vancomycin-susceptibility regulator 1) encoding a PadR family transcriptional regulator located in the putative operon , which is conserved in other spp as well. This is the first report linking a homologue ( ) to antimicrobial resistance in a Gram-negative organism. We provide evidence to support that acts as a negative regulator of and that upregulation is observed in vancomycin-selected mutants. Vancomycin-selected mutants also demonstrated reduced cell length indicating that cell wall synthesis is affected. ORF551 is a membrane-spanning protein with a small phage shock protein conserved domain. We hypothesize that since vancomycin-resistance is a function of membrane permeability in Gram-negative organisms, it is likely that the antimicrobial resistance mechanism in the vancomycin-selected mutants involves altered drug permeability.