ABSTRACT
Objectives: Pseudomonas aeruginosa has been globally implicated in healthcare-associated infection. The susceptibility pattern of clinical isolates of P. aeruginosa to anti-pseudomonal antibiotics is reported. Materials and Methods: Clinical samples, namely blood, urine, tracheal aspirate, cerebrospinal fluid (CSF), wound swabs, high vaginal swabs, eye, and ear exudates were obtained from patients, processed and identified using standard microbiological protocols. Antibiotic susceptibility testing was undertaken using the Kirby Bauer Disc diffusion method. Results were reported following the Clinical and Laboratory Standards Institute guidelines. Results: Of 104 P. aeruginosa isolates identified, males (52.88%) had a higher incidence of infection than female (47.11%) patients. The highest prevalence was recorded from wound swabs [46 (44.23%)] followed by ear exudates [23 (22.12%)], urine [22 (21.15%)], while eye exudates and samples from the CSF yielded the least [1 (0.96% each)]. From the antibiogram, imipenem had the highest antibiotic activity (91.3%) followed by polymyxin B (84.6%). The isolates exhibited the highest resistance to ceftazidime (73.1%) and piperacillin-tazobactam (61.5%). The antibiotic susceptibility pattern of P. aeruginosa isolates revealed 7.69% susceptible, 26% resistant, 61% multidrug resistance (MDR), 5% extremely drug resistance (XDR), and an absence (0%) of pandrug-resistant phenotypes. Conclusion: The study recorded alarmingly high cases of MDR and some XDR phenotypes of P. aeruginosa in University of Port Harcourt Teaching Hospital. It will help identify existing gaps in antimicrobial resistance surveillance and assist in improving public health policies regarding antibiotic stewardship, initiatives, and interventions.
ABSTRACT
Pathogenic and commensal Neisseria species produce an Adhesin Complex Protein, which was first characterised in Neisseria meningitidis (Nm) as a novel surface-exposed adhesin with vaccine potential. In the current study, the crystal structure of a recombinant (r)Nm-ACP Type I protein was determined to 1.4 Å resolution: the fold resembles an eight-stranded ß-barrel, stabilized by a disulphide bond between the first (Cys38) and last (Cys121) ß-strands. There are few main-chain hydrogen bonds linking ß4-ß5 and ß8-ß1, so the structure divides into two four-stranded anti-parallel ß-sheets (ß1-ß4 and ß5-ß8). The computed surface electrostatic charge distribution showed that the ß1-ß4 sheet face is predominantly basic, whereas the ß5-ß8 sheet is apolar, apart from the loop between ß4 and ß5. Concentrations of rNm-ACP and rNeisseria gonorrhoeae-ACP proteins ≥0.25 µg/ml significantly inhibited by ~80-100% (P<0.05) the in vitro activity of human lysozyme (HL) over 24 h. Specificity was demonstrated by the ability of murine anti-Neisseria ACP sera to block ACP inhibition and restore HL activity. ACP expression conferred tolerance to HL activity, as demonstrated by significant 3-9 fold reductions (P<0.05) in the growth of meningococcal and gonococcal acp gene knock-out mutants in the presence of lysozyme. In addition, wild-type Neisseria lactamica treated with purified ACP-specific rabbit IgG antibodies showed similar fold reductions in bacterial growth, compared with untreated bacteria (P<0.05). Nm-ACPI is structurally similar to the MliC/PliC protein family of lysozyme inhibitors. However, Neisseria ACP proteins show <20% primary sequence similarity with these inhibitors and do not share any conserved MliC/PliC sequence motifs associated with lysozyme recognition. These observations suggest that Neisseria ACP adopts a different mode of lysozyme inhibition and that the ability of ACP to inhibit lysozyme activity could be important for host colonization by both pathogenic and commensal Neisseria organisms. Thus, ACP represents a dual target for developing Neisseria vaccines and drugs to inhibit host-pathogen interactions.
