Dual Role of gnaA in Antibiotic Resistance and Virulence in Acinetobacter baumannii

Abstract

Acinetobacter baumannii is an important Gram-negative pathogen in hospital-related infections. However, treatment options for A. baumannii infections have become limited due to multidrug resistance. Bacterial virulence is often associated with capsule genes found in the K locus, many of which are essential for biosynthesis of the bacterial envelope. However, the roles of other genes in the K locus remain largely unknown. From an in vitro evolution experiment, we obtained an isolate of the virulent and multidrug-resistant A. baumannii strain MDR-ZJ06, called MDR-ZJ06M, which has an insertion by the ISAba16 transposon in gnaA (encoding UDP-N-acetylglucosamine C-6 dehydrogenase), a gene found in the K locus. The isolate showed an increased resistance toward tigecycline, whereas the MIC decreased in the case of carbapenems, cephalosporins, colistin, and minocycline. By using knockout and complementation experiments, we demonstrated that gnaA is important for the synthesis of lipooligosaccharide and capsular polysaccharide and that disruption of the gene affects the morphology, drug susceptibility, and virulence of the pathogen.

The UDP‐GalNAcA biosynthesis genes gna‐gne2 are required to maintain cell envelope integrity and in vivo fitness in multi‐drug resistant Acinetobacter baumannii

“…Despite major differences in their K locus (AB0057 vs MDR‐ZJ06), where wzx , qnr and a homolog of gna are the only genes in common from the variable region (Kenyon and Hall, ), the findings described by Xu et al . () are in agreement with the results described in this report, reinforcing the idea that gna , and its homologs, play a pivotal role in the pathobiology of A . baumannii that goes beyond capsule production.…”

“…During the revision of this article, a study analyzing the role of gnaA (homolog of the gna described herein) in the physiology of the A. baumannii MDR strain MDR‐ZJ06 was reported (Xu et al , ). Despite major differences in their K locus (AB0057 vs MDR‐ZJ06), where wzx , qnr and a homolog of gna are the only genes in common from the variable region (Kenyon and Hall, ), the findings described by Xu et al .…”

“…During the revision of this article, a study analyzing the role of gnaA (homolog of the gna described herein) in the physiology of the A. baumannii MDR strain MDR-ZJ06 was reported (Xu et al, 2019). Despite major differences in their K locus (AB0057 vs MDR-ZJ06), where wzx, qnr and a homolog of gna are the only genes in common from the variable region (Kenyon and Hall, 2013), the findings described by Xu et al (2019) are in agreement with the results described in this report, reinforcing the idea that gna, and its homologs, play a pivotal role in the pathobiology of A. baumannii that goes beyond capsule production.…”

The mismatch repair system (mutS and mutL) in Acinetobacter baylyi ADP1

“…The final cultures were stored at − 80°C. The genomic DNA was extracted and sequenced as previously described [28]. Briefly, the genomic DNA was extracted using a QIAamp DNA Mini Kit (Qiagen Valencia, CA).…”

Recent Advances in Genetic Tools for Acinetobacter baumannii

“…The methods of Choi and Schweizer have been adapted for use in A. baumannii (De Silva and Kumar, 2018;De Silva et al, 2020) and includes the initial step of Splicing Overlap Extension (SOE), which introduces an antibiotic resistance gene flanked by Flp Recombinase Target (FRT) sites into the flanking homologous regions of the target gene to allow for selection of recombinants and antibiotic gene removal, respectively (Choi and Schweizer, 2005). Applications in clinical isolates using this method ( Supplementary Table 1) have been successful depending on the type of selection and counter-selection markers used (Trebosc et al, 2016(Trebosc et al, , 2019Xu Q. et al, 2019).…”