Acinetobacter baumannii is considered one of the most persistent pathogens responsible for nosocomial infections. Due to the emergence of multidrug resistant strains, as well as high morbidity and mortality caused by this pathogen, A. baumannii was placed on the World Health Organization (WHO) drug-resistant bacteria and antimicrobial resistance research priority list. This review summarizes current studies on mechanisms that protect A. baumannii against multiple stresses caused by the host immune response, outside host environment, and antibiotic treatment. We particularly focus on the ability of A. baumannii to survive long-term desiccation on abiotic surfaces and the population heterogeneity in A. baumannii biofilms. Insight into these protective mechanisms may provide clues for the development of new strategies to fight multidrug resistant strains of A. baumannii.

The small heat shock proteins are ubiquitous stress proteins proposed to increase cellular tolerance to heat shock conditions. We isolated IbpA, the Escherichia coli small heat shock protein, and tested its ability to keep thermally inactivated substrate proteins in a disaggregation competent state. We found that the presence of IbpA alone during substrate thermal inactivation only weakly influences the ability of the bi-chaperone Hsp70-Hsp100 system to disaggregate aggregated substrate. Similar minor effects were observed for IbpB alone, the other E. coli small heat shock protein. However, when both IbpA and IbpB are simultaneously present during substrate inactivation they efficiently stabilize thermally aggregated proteins in a disaggregation competent state. The properties of the aggregated protein substrates are changed in the presence of IbpA and IbpB, resulting in lower hydrophobicity and the ability of aggregates to withstand sizing chromatography conditions. IbpA and IbpB form mixed complexes, and IbpA stimulates association of IbpB with substrate.

The roles of the Escherichia coli IbpA and IbpB chaperones in protection of heat-denatured proteins against irreversible aggregation in vivo were investigated. Overproduction of IbpA and IbpB resulted in stabilization of the denatured and reversibly aggregated proteins (the S fraction), which could be isolated from E. coli cells by sucrose gradient centrifugation. This finding is in agreement with the present model of the small heat-shock proteins’ function, based mainly on in vitro studies. Deletion of the ibpAB operon resulted in almost twofold increase in protein aggregation and in inactivation of an enzyme (fructose-1,6-biphosphate aldolase) in cells incubated at 50 °C for 4 h, decreased efficiency of the removal of protein aggregates formed during prolonged incubation at 50 °C and affected cell viability at this temperature. IbpA/B proteins were not needed for removal of protein aggregates or for the enzyme protection/renaturation in cells heat shocked at 50 °C for 15 min. These results show that the IbpA/B proteins are required upon an extreme, long-term heat shock. Overproduction of IbpA but not IbpB caused an increase of the level of β-lactamase precursor, which was localized in the S fraction, together with the IbpA protein, which suggests that the unfolded precursor binds to IbpA but not to IbpB. Although in the wild-type cells both E. coli small heat-shock proteins are known to localize in the S fraction, only 2% of total IbpB co-localized with the aggregated proteins in the absence of IbpA, while in the absence of IbpB, the majority of IbpA was present in the aggregates fraction.

Klebsiella pneumoniae is one of the most common pathogens responsible for infections, including pneumonia, urinary tract infections, and bacteremias. The increasing prevalence of multidrug-resistant K. pneumoniae was recognized in 2017 by the World Health Organization as a critical public health threat. Heteroresistance, defined as the presence of a subpopulation of cells with a higher MIC than the dominant population, is a frequent phenotype in many pathogens. Numerous reports on heteroresistant K. pneumoniae isolates have been published in the last few years. Heteroresistance is difficult to detect and study due to its phenotypic and genetic instability. Recent findings provide strong evidence that heteroresistance may be associated with an increased risk of recurrent infections and antibiotic treatment failure. This review focuses on antibiotic heteroresistance mechanisms in K. pneumoniae and potential therapeutic strategies against antibiotic heteroresistant isolates.