Phenotypic changes associated with Colistin resistance due to Lipopolysaccharide loss in Acinetobacter baumannii. Issue 1 (31st December 2018)

• Record Type: Journal Article
• Authors: Carretero-Ledesma, Marta; García-Quintanilla, Meritxell; Martín-Peña, Reyes; Pulido, Marina R.; Pachón, Jerónimo; McConnell, Michael J.
• Is Part Of: Virulence. Volume 9:Issue 1(2018)
• Page Start: 930
• Page End: 942
• Publication Date: 2018-12-31
• Subjects: Acinetobacter baumannii -- colistin -- fitness -- lipopolysaccharide -- virulence; Virulence (Microbiology) -- Periodicals; Bacterial diseases -- Periodicals; Molecular microbiology -- Periodicals; 579.05
• DOI: 10.1080/21505594.2018.1460187
• Languages: English
• ISSNs: 2150-5608

Abstract

ABSTRACT: Acinetobacter baumannii can acquire resistance to colistin via complete loss of lipopolysaccharide (LPS) biosynthesis due to mutations in the lpxA, lpxC and lpxD genes. However, although colistin is increasingly being used for the treatment of multidrug resistant infections, very few A. baumannii clinical isolates develop colistin resistance through loss of LPS biosynthesis. This may suggest that LPS loss affects virulence traits that play a role in the transmission and pathogenesis of A. baumannii . In this study we characterize multiple virulence phenotypes of colistin resistant, LPS-deficient derivatives of the ATCC 19606 strain and five multidrug resistant clinical isolates and their colistin resistant, LPS-deficient derivatives. Our results indicate that LPS loss results in growth defects compared to the parental strain in vitro both in laboratory media and human serum (competition indices of 0.58 and 7.0 × 10 −7, respectively) and reduced ability to grow and disseminate in vivo (competition index 6.7 × 10 −8 ). Infection with the LPS-deficient strain resulted in lower serum levels of pro-inflammatory cytokines TNF-α and IL-6 compared to the parent strain, and was less virulent in a mouse model of disseminated sepsis. LPS loss also significantly affected biofilm production, surface motility, growth under iron limitation and susceptibility to multiple disinfectants used in the clinical setting. These results demonstrate that LPS loss has a significant effect on multiple virulence traits, and may provide insight into the low incidence of colistin resistant strains lacking LPS that have been reported in the clinical setting.