Antibiotic Resistance Characteristics of Pseudomonas aeruginosa Isolated from Keratitis in Australia and India

Abstract

This study investigated genomic differences in Australian and Indian Pseudomonas aeruginosa isolates from keratitis (infection of the cornea). Overall, the Indian isolates were resistant to more antibiotics, with some of those isolates being multi-drug resistant. Acquired genes were related to resistance to fluoroquinolones, aminoglycosides, beta-lactams, macrolides, sulphonamides, and tetracycline and were more frequent in Indian (96%) than in Australian (35%) isolates (p = 0.02). Indian isolates had large numbers of gene variations (median 50,006, IQR = 26,967–50,600) compared to Australian isolates (median 26,317, IQR = 25,681–33,780). There were a larger number of mutations in the mutL and uvrD genes associated with the mismatch repair (MMR) system in Indian isolates, which may result in strains losing their efficacy for DNA repair. The number of gene variations were greater in isolates carrying MMR system genes or exoU. In the phylogenetic division, the number of core genes were similar in both groups, but Indian isolates had larger numbers of pan genes (median 6518, IQR = 6040–6935). Clones related to three different sequence types—ST308, ST316, and ST491—were found among Indian isolates. Only one clone, ST233, containing two strains was present in Australian isolates. The most striking differences between Australian and Indian isolates were carriage of exoU (that encodes a cytolytic phospholipase) in Indian isolates and exoS (that encodes for GTPase activator activity) in Australian isolates, large number of acquired resistance genes, greater changes to MMR genes, and a larger pan genome as well as increased overall genetic variation in the Indian isolates.

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“…All of the isolates carried a β-lactam resistance gene (bla PAO ), most of the Australian isolates carried bla OXA-396 , while other β-lactam resistance genes were also seen in both Australian and Indian isolates (e.g., bla OXA-486 , bla OXA-488 , bla OXA-396 , and bla OXA-50 ), although much less commonly. Resistance rates were 78% for imipenem and 57% for ceftazidime, and 58% for imipenem and 50% for ceftazidime in Indian and Australian isolates, respectively [73].…”

“…Some reports suggest that there may be an association between virulence and antibiotic resistance in P. aeruginosa isolates, as the carriage of the exoU genes was shown to correlate with resistance to aminoglycosides and fluoroquinolones. A possible explanation was that the genomic island carrying exoU may also contain resistance-determinant genes [73,74].…”

“…Possible clinical manifestations include pneumonia (mainly ventilator-associated (VAP; 10-30%), while the community-acquired form is far less common (CAP; 1-3%)), skin and soft tissue infections associated with burns and surgeries (8-10%), "hot tub" folliculitis, "swimmer's ear" otitis externa, eye infections (keratitis), urinary tract infections (UTI; 813.8615%), endocarditis, and bacteremia/sepsis (central-line-associated or often secondary to pneumonia) [125][126][127][128][129][130]133]. Among bacterial pathogens responsible for contact lensassociated keratitis, P. aeruginosa has the worst disease manifestation (i.e., the development of a corneal ulcer, which may occur in 40-60% of cases), leading to poor outcomes, the fulminant destruction of the cornea, and vision loss [73,134,135]. The mortality rate of pseudomonad infections is a big concern among immunocompromised and hospitalized patients, which is around 25-39% for pneumonia and 18-61% for bacteremia, while these rates may be higher (40-70%) in case of MDR isolates [136][137][138].…”

“…They have also found a positive association between the MDR/XDR phenotype and the presence of hemolysin, the exoU gene, and integrase I [243]. In the study of Khan et al, the resistance characteristics of keratitis-causing P. aeruginosa isolates, originating from Australia and India, were compared [73]. All of the isolates carried a β-lactam resistance gene (bla PAO ), most of the Australian isolates carried bla OXA-396 , while other β-lactam resistance genes were also seen in both Australian and Indian isolates (e.g., bla OXA-486 , bla OXA-488 , bla OXA-396 , and bla OXA-50 ), although much less commonly.…”

“…Even though there is growing literature available on the topic, there is no consensus on the most common mechanisms of resistance contributing to the emergence of Car-R/Ceph-S isolates. There are wide-ranging differences in the prevalence of carbapenemases (especially for MBLs), and this may affect the susceptibility to cephalosporins as well [73,[230][231][232][233][234][235][236][237][238][239][240][241][242][243][244]. Khalili et al proposed that the detection of Car-R/Ceph-S isolates is dependent on the absence of carbapenemases [240].…”