Increased ompW and ompA expression and higher virulence of Acinetobacter baumannii persister cells

Abstract

Background Acinetobacter baumannii is one of the main causes of healthcare-associated infections that threaten public health, and carbapenems, such as meropenem, have been a therapeutic option for these infections. Therapeutic failure is mainly due to the antimicrobial resistance of A. baumannii, as well as the presence of persister cells. Persisters constitute a fraction of the bacterial population that present a transient phenotype capable of tolerating supra-lethal concentrations of antibiotics. Some proteins have been suggested to be involved in the onset and/or maintenance of this phenotype. Thus, we investigated the mRNA levels of the adeB (AdeABC efflux pump component), ompA, and ompW (outer membrane proteins) in A. baumannii cells before and after exposure to meropenem. Results We found a significant increase (p-value < 0.05) in the expression of ompA (> 5.5-fold) and ompW (> 10.5-fold) in persisters. However, adeB did not show significantly different expression levels when comparing treated and untreated cells. Therefore, we suggest that these outer membrane proteins, especially OmpW, could be part of the mechanism of A. baumannii persisters to deal with the presence of high doses of meropenem. We also observed in the Galleria mellonella larvae model that persister cells are more virulent than regular ones, as evidenced by their LD50 values. Conclusions Taken together, these data contribute to the understanding of the phenotypic features of A. baumannii persisters and their relation to virulence, as well as highlight OmpW and OmpA as potential targets for drug development against A. baumannii persisters.

Calcium Induces the Cleavage of NopA and Regulates the Expression of Nodulation Genes and Secretion of T3SS Effectors in Sinorhizobium fredii NGR234

“…As reported in S. fredii USDA257, we also detected in NGR234 that calcium downregulated the expression of an outer membrane protein, putative OmpW (NGR_a02570) ( Table 3 ). OmpW might be involved in the membrane integrity in USDA257 [ 29 ], but in the case of pathogenic bacteria, such as Acinetobacter baumannii , the increased expression of this protein seems to be involved in the antibiotic resistance mechanism together with OmpA [ 34 ]. As mentioned before, NGR234_b22780 is the most upregulated gene in the presence of calcium and codes for a putative small transmembrane protein with an unknown functional domain.…”

Multidrug-Resistant and Extensively Drug-Resistant Acinetobacter baumannii Causing Nosocomial Meningitis in the Neurological Intensive Care Unit

“…The adherence group was presented by the ompA gene detected in all strains. A significantly increasing expression of the ompA gene in persisters was recently shown, which proposes ompA as a potential target for drug development against A. baumannii persisters [ 49 ]. Additionally, the ptmA gene was detected in two strains of ST2 and ST7; this is in agreement with the opinion that this virulence factor is quite rare [ 50 ].…”

Antibiotic discovery with artificial intelligence for the treatment of Acinetobacter baumannii infections

“…The extensive functions of outer membrane proteins (OMPs) in GNB have led to their identi cation as potential drug targets [6]. Among the OMPs, outer membrane protein W (OmpW) is a porin playing a pivotal role in the uptake of nutritional substances such as iron [7]. Several studies have highlighted the relevance of OmpW as a potential drug target in GNB.…”