Abstract

The rise in the number of antibiotic-resistant bacteria has become a serious threat to health, making it important to identify, characterize and optimize new molecules to help us to overcome the infections they cause. It is well known that Acinetobacter baumannii has a significant capacity to evade the actions of antibacterial drugs, leading to its emergence as one of the bacteria responsible for hospital and community-acquired infections. Nonetheless, how this pathogen infects and survives inside the host cell is unclear. In this study, we analyze the time-resolved transcriptional profile changes observed in human epithelial HeLa cells after infection by A. baumannii, demonstrating how it survives in host cells and starts to replicate 4 h post infection. These findings were achieved by sequencing RNA to obtain a set of Differentially Expressed Genes (DEGs) to understand how bacteria alter the host cells’ environment for their own benefit. We also determine common features observed in this set of genes and identify the protein–protein networks that reveal highly-interacted proteins. The combination of these findings paves the way for the discovery of new antimicrobial candidates for the treatment of multidrug-resistant bacteria.

Highlights

  • The growing resistance of pathogens is a matter of real concern today

  • We investigated whether A. baumannii is able to survive inside epithelial cells

  • Our results revealed that A. baumannii was able to colonize 0.3% of the HeLa cells and started to slowly replicate at 4 hours post-infection (HPI), reaching 2.3% at 6 h (Figure 1a)

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Summary

Introduction

The growing resistance of pathogens is a matter of real concern today. several authors have described drug-resistant bacteria for which few, or no, treatments are available [1]. The failure to identify new antibiotics or molecules to fight these bacteria is becoming a threat to health systems across the globe [2]. In this context, understanding how pathogen bacteria can survive inside a host is crucial [3]. A. baumannii is considered to be one of the most important bacteria pathogens. These are commonly referred to as ESKAPE organisms (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter), and have the capacity to evade the actions of antibacterial drugs [4] and survive prolonged and harsh treatments. Thanks to a small genomic region of 86 kilobases containing

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