Abstract
Acinetobacter baumannii (Ab) is one of the most important pathogens associated with nosocomial infections, especially pneumonia. Interest in the Quorum network, i.e., Quorum Sensing (QS)/Quorum Quenching (QQ), in this pathogen has grown in recent years. The Quorum network plays an important role in regulating diverse virulence factors such as surface motility and bacterial competition through the type VI secretion system (T6SS), which is associated with bacterial invasiveness. In the present study, we investigated 30 clinical strains of A. baumannii isolated in the “II Spanish Study of A. baumannii GEIH-REIPI 2000-2010” (Genbank Umbrella Bioproject PRJNA422585), a multicentre study describing the relationship between the Quorum network in A. baumannii and the development of pneumonia and associated bacteraemia. Expression of the aidA gene (encoding the AidA protein, QQ enzyme) was lower (P < 0.001) in strains of A. baumannii isolated from patients with bacteraemic pneumonia than in strains isolated from patients with non-bacteraemic pneumonia. Moreover, aidA expression in the first type of strain was not regulated in the presence of environmental stress factors such as the 3-oxo-C12-HSL molecule (substrate of AidA protein, QQ activation) or H2O2 (inhibitor of AidA protein, QS activation). However, in the A. baumannii strains isolated from patients with non-bacteraemic pneumonia, aidA gene expression was regulated by stressors such as 3-oxo-C12-HSL and H2O2. In an in vivo Galleria mellonella model of A. baumannii infection, the A. baumannii ATCC 17978 strain was associated with higher mortality (100% at 24 h) than the mutant, abaI-deficient, strain (carrying a synthetase enzyme of Acyl homoserine lactone molecules) (70% at 24 h). These data suggest that the QS (abaR and abaI genes)/QQ (aidA gene) network affects the development of secondary bacteraemia in pneumonia patients and also the virulence of A. baumannii.
Highlights
Acinetobacter baumannii is a major cause of hospital-acquired infections associated with high mortality rates (Fuchs, 2016),s usually affecting patients in Intensive Care Units (ICU)
The values of the Relative Expression (RE) of the abaR and aidA genes (Quorum network) in the presence of 3-Oxo-C12-HSL (Inhibition of the Quorum Sensing system (QS)) and H2O2 (Activation of the QS), obtained by RT-qPCR of the 13 isolates of A. baumannii from patients with pneumonia are shown in Table 3, expressed as STRAINS OF A. baumannii ISOLATED FROM COLONIZED PATIENTS
We analyzed the expression of Quorum network (QS/QQ) genes that differed between genomes of clinical isolates of A. baumannii, abaR and abaI (QS system) and aidA (QQ mechanism) in relation to clinical features of pneumonia and bacteraemia
Summary
Acinetobacter baumannii is a major cause of hospital-acquired infections associated with high mortality rates (Fuchs, 2016),s usually affecting patients in Intensive Care Units (ICU) (del Mar Tomas et al, 2005; Lee et al, 2017). A. baumannii causes infections such as pneumonia or, to a lesser extent, serious infections of the bloodstream (around 10% of clinical isolates of A. baumannii cause bacteraemia) (Cisneros and Rodríguez-Baño, 2002; El Kettani et al, 2017) The success of this bacterium as a nosocomial pathogen, has been attributed to the following factors, amongst others: (i) high genetic versatility, facilitating rapid adaptation to stressful or unfavorable situations (Gayoso et al, 2014; Trastoy et al, 2018); (ii) ability to acquire new genes horizontally by the acquisition of plasmids and phages (López et al, 2018); (iii) ability to persist for a long time on animate and inanimate surfaces (resistance to desiccation) (Gayoso et al, 2014), which is generally attributed to biofilm formation; (iv) resistance to antimicrobial agents, including broad-spectrum antibiotics such as carbapenems, colistin, and tigecycline (Fernández-Cuenca et al, 2015), as well as to disinfectants and biocides (FernándezGarcía et al, 2018); and (v) high virulence (colonization, invasiveness, and cytotoxicity) (Rumbo et al, 2014; Wong et al, 2017). In February, 2017, the World Health Organization (WHO) published a list of “priority pathogens.” The list includes antibiotic resistant bacteria, considered a serious threat to human health and for which new antibiotics are urgently needed, and is headed by carbapenem-resistant A. baumannii (Tacconelli et al, 2018)
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