Mucin acts as a nutrient source and a signal for the differential expression of genes coding for cellular processes and virulence factors in Acinetobacter baumannii.

Emily J Ohneck,Steven E Fiester,Maeva L Metz,Luis A Actis,Gabriella M Simeone,Brock A Arivett,Cecily R Wood,Suresh Yenugu

doi:10.1371/journal.pone.0190599

Abstract

The capacity of Acinetobacter baumannii to persist and cause infections depends on its interaction with abiotic and biotic surfaces, including those found on medical devices and host mucosal surfaces. However, the extracellular stimuli affecting these interactions are poorly understood. Based on our previous observations, we hypothesized that mucin, a glycoprotein secreted by lung epithelial cells, particularly during respiratory infections, significantly alters A. baumannii’s physiology and its interaction with the surrounding environment. Biofilm, virulence and growth assays showed that mucin enhances the interaction of A. baumannii ATCC 19606T with abiotic and biotic surfaces and its cytolytic activity against epithelial cells while serving as a nutrient source. The global effect of mucin on the physiology and virulence of this pathogen is supported by RNA-Seq data showing that its presence in a low nutrient medium results in the differential transcription of 427 predicted protein-coding genes. The reduced expression of ion acquisition genes and the increased transcription of genes coding for energy production together with the detection of mucin degradation indicate that this host glycoprotein is a nutrient source. The increased expression of genes coding for adherence and biofilm biogenesis on abiotic and biotic surfaces, the degradation of phenylacetic acid and the production of an active type VI secretion system further supports the role mucin plays in virulence. Taken together, our observations indicate that A. baumannii recognizes mucin as an environmental signal, which triggers a response cascade that allows this pathogen to acquire critical nutrients and promotes host-pathogen interactions that play a role in the pathogenesis of bacterial infections.

Highlights

Acinetobacter baumannii causes several types of severe infections in compromised individuals [1, 2]
For this purpose we adapted protocols used for the study of P. aeruginosa, another relevant human respiratory pathogen, that are based on the addition of commercially available porcine gastric mucin (PGM) to culture media based on the observation that MUC5AC is the major component of gastric and respiratory mucins [19, 44,45,46,47]
The addition of exogenous mucin to sterile polarized cells did not cause any apparent damage or change to the cell layers when compared to untreated, sterile polarized A549 cells (Fig 1A, panels a and c). These observations are consistent with the effect mucin has on American Type Culture Collection (ATCC) 19606T bacteria when co-cultured with submerged A549 monolayers

Summary

Introduction

Acinetobacter baumannii causes several types of severe infections in compromised individuals [1, 2]. Patients infected with A. baumannii have a mortality rate ranging from 20% to 50%, which may be attributed to cellular functions such as capsule production, biofilm formation, the expression of a variety of nutrient and iron acquisition pathways, the ability to cope with environmental stress, and the acquisition and expression of multidrug resistance (MDR) genes [11]. This problem is further compounded by our limited understanding of the mechanisms by which A. baumannii interacts with the human host. A. baumannii’s interaction with mucin merits further study

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