Investigation of the Virulence Factors and Molecular Characterization of the Clonal Relations of Multidrug-Resistant Acinetobacter baumannii Isolates

Abstract

Multidrug-resistant (MDR) Acinetobacter baumannii infections are a great public health concern and demand continuous surveillance and antibiotic stewardship. Virulence traits and the pathogenicity of Acinetobacter are less studied compared with the molecular epidemiological and antibiotic resistance profile of this organism. In our present study, we investigated the primary characteristics contributing to the virulence of MDR A. baumannii isolates and compared them with avirulent isolates. A total of 32 well-characterized MDR A. baumannii clinical isolates and 22 avirulent isolates from a healthy individual were subjected to multilocus sequence typing and polymerase chain reaction (PCR) for a variety of biofilm-associated genes. Additionally, a number of in vitro tests were performed to determine virulence properties. Isolates were found to relate to six sequence types (STs) in which the dominant sequence was ST557 in clinical isolates, followed by ST195 and ST208. However, ST557 and ST222 were absent in avirulent isolates. All STs belonged to clonal complex 2 and clonal lineage 2, which is considered to be a universal clone. PCR analysis showed that most clinical isolates were positive for biofilm-forming genes, such as csu and bap, and also carried pga and ompA genes, which were less common in avirulent isolates. Biofilm formation, phospholipase C production, hemolytic activity, and acinetobactin production occurred significantly more frequently in clinical isolates compared with avirulent isolates. Though A. baumannii clonal lineages showed common virulence traits, they differed in virulent phenotype expression. These findings further support previous studies indicating that A. baumannii is a versatile pathogen with an ability to acquire iron and survive in iron-limiting conditions, highlighting the acinetobactin-mediated iron acquisition mechanisms involved in the pathogenesis of A. baumannii infections.

Wza gene knockout decreases Acinetobacter baumannii virulence and affects Wzy-dependent capsular polysaccharide synthesis

“…Additionally, biofilm formation, phospholipase C production, hemolytic activity, and toxin production are higher than in non-virulent strains. This indicates that clinically isolated ST195 strains possess high virulence [34].…”

Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options

“…Acinetobacter baumannii also has iron siderophores and acinetobactin, the best-characterized A. baumannii siderophore, is a mixed type siderophore with an oxazoline ring derived from threonine (McConnell et al, 2013). Acinetobactin is an A. baumannii virulence factor (Gaddy et al, 2012; Penwell et al, 2012; Megeed et al, 2016). Impaired acinetobactin biosynthesis and transport functions significantly reduce the ability of A. baumannii ATCC 19606 cells to persist within epithelial cells and cause cell damage and animal death (Gaddy et al, 2012).…”

“…Mutation in the entA gene, which is essential for biosynthesis of the acinetobactin precursor 2,3-dihydroxybenzoic acid, also significantly reduces the capacity of A. baumannii ATCC 19606 cells to persist within human alveolar epithelial cells and diminishes the ability to infect and kill Galleria mellonella larvae (Penwell et al, 2012). One study showed that acinetobactin production occurs significantly more frequently in MDR A. baumannii isolates than that in avirulent isolates (Megeed et al, 2016). …”

Antibiotic-Resistant Acinetobacter baumannii Is Susceptible to the Novel Iron-Sequestering Anti-infective DIBI In Vitro and in Experimental Pneumonia in Mice

“…The production of the siderophore acinetobactin and its role in Fe acquisition and the virulence of LAC-4 and ATCC 19606 has been described (8,21), and acinetobactin synthesis and associated transport genes have been mapped in various isolates, including LAC-4, ATCC 17978, and ATCC 19606 (22,23). It is interesting to note in this regard that MDR isolates have been reported to typically possess the acinetobactin Fe acquisition virulence system (9).…”

“…Iron acquisition is a virulence determinant for A. baumannii with its acinetobactin iron siderophore acquisition system being more prevalent in MDR isolates (1,8,9). Gallium, a nonfunctional analogue of Fe that inhibits A. baumannii growth and biofilm formation in vitro by displacing functional iron (10,11), has also been shown to suppress A. baumannii experimental pneumonia in mice (12).…”