Coxiella burnetii Pathogenesis: Emphasizing the Role of the Autophagic Pathway.

Coxiella burnetii (C. burnetii), the etiological agent of the Q fever disease, ranks among the most sporadic and persistent global public health concerns. Ruminants are the principal source of human infections and diseases present in both acute and chronic forms. This bacterium is an intracellular pathogen that can survive and reproduce under acidic (pH 4 to 5) and harsh circumstances that contain Coxiella-containing vacuoles. By undermining the autophagy defense system of the host cell, C. burnetii is able to take advantage of the autophagy pathway, which allows it to improve the movement of nutrients and the membrane, thereby extending the vacuole of the reproducing bacteria. For this method to work, it requires the participation of many bacterial effector proteins. In addition, the precise and prompt identification of the causative agent of an acute disease has the potential to delay the onset of its chronic form. Moreover, to make accurate and rapid diagnoses, it is necessary to create diagnostic devices. This review summarizes the most recent research on the epidemiology, pathogenesis, and diagnosis approaches of C. burnetii. This study also explored the complicated relationships between C. burnetii and the autophagic pathway, which are essential for intracellular reproduction and survival in host cells for the infection to be effective.

Antibiotic Susceptibility and Biofilm Formation of Bacterial Isolates Derived from Pediatric Patients with Cystic Fibrosis from Tehran, Iran.

Cystic fibrosis (CF) is a genetic disease with a high rate of morbidity and mortality. Children with CF commonly suffer from recurrent and persistent pulmonary tract infections caused by diverse bacterial pathogens. This study aimed to investigate the prevalence, antimicrobial susceptibility, and biofilm formation of bacterial isolates in pediatric patients with CF. The study population of this cross-sectional study included 8,908 children suspected to have CF by clinical manifestations from March 2015 to August 2017 who were referred to the Tehran Pediatric Central Hospital, Iran. The tests carried out for each participant included screening sweat test, sputum culture, antibiotic susceptibility test using Kirby-Bauer disk diffusion method, and biofilm formation in microtiter plates method. Based onclinical examination and screening sweat test, 183 (2.05 %( out of 8,908 children, were positive for CF. The mean age of children was estimated at 2.93 years, and the majority of them were male (n=103, 56.2%). No gender-specific difference was observed in CF disease in this study (P>0.05). In addition, the results of sputum culture showed that 153 (83.6%) microorganisms (bacteria and fungi) were collected from CF patients. Normal flora was isolated in 30 (16.4%) patients and more than one bacterial species were isolated in 7.2% of patients. The obtained results indicated that Pseudomonas aeruginosa was the most prevalent isolated bacteria followed by Staphylococcus aureus, and Klebsiella pneumoniae. Based on the antibiotic susceptibility test results, P. aeruginosa and piperacillin/tazobactam had the highest (11.7%) and the lowest (2.3%) resistance rate against gentamicin, respectively. However, all K. pneumoniae isolates were resistant to Cefotaxime. Among S. aureus isolates, 83.4% and 16.6% were methicillin-susceptible Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus respectively. Concerning biofilm formation, 76%, 67%, and 72.5% of P. aeruginosa, S. aureus, and K. pneumoniae isolates were biofilm producers, respectively. Based on the study results, P. aeruginosa was the dominant pathogen in pediatric patients with CF from Tehran, Iran, and most of the pathogens were biofilm producers. No severe antibiotic resistance was observed in the isolates; however, the anti-microbial resistance profile should be carefully checked in CF patients on a regular basis.

Clonal relatedness and resistance characteristics of OXA-24 and -58 producing carbapenem-resistant Acinetobacter baumannii isolates in Tehran, Iran.

AIMS: The present study was conducted to investigate the mechanism of carbapenem resistance and the molecular epidemiology of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates collected from two nearby hospitals in Tehran, Iran. METHODS AND RESULTS: A total of 180 CRAB isolates were studied. Antimicrobial susceptibility testing was performed using disk diffusion and Epsilometer tests. The detection of OXA-23, -24 and -58 was implemented for all isolates using polymerase chain reaction. Subsequently, isolates harbouring OXA-24 and -58 were investigated for the presence of resistance determinants of Ambler class A, metallo-ß-lactamases (MBLs), and carbapenem-hydrolysing class D ß-lactamases, ISAba1, and the genetic relatedness between them was analysed using pulsed-field gel electrophoresis (PFGE). All isolates were found to be resistant to imipenem with a MIC of ≥8 µg ml-1 and were susceptible to colistin with a MIC of ≤1·5 µg ml-1 . Sixty percent of the isolates had OXA-23. OXA-24 and -58 were detected in 31 of 180 CRAB isolates. These chosen isolates were devoid of MBLs and blaSHV , blaC TX-M , blaVEB ESBL genes. The PER determinant was detected in 38% of isolates as the most common extended spectrum ß-lactamases (ESBLs). Of these isolates, 51·6% had OXA-23, and ISAba1 was found to be upstream of OXA-23 and OXA-51 in 16 and 8 isolates, respectively. The band patterns produced by PFGE showed nine clonal pulsotypes distributed between the two hospitals. CONCLUSION: The findings showed that the refractory CRAB isolates were transmitted intra- and inter-hospital, particularly in the ICU due to shortcomings in infection control surveillance. SIGNIFICANCE AND IMPACT OF THE STUDY: Carbapenem resistance is a substantial threat in the treatment of infections caused by A. baumannii due to limitations in the therapeutic options.

The impact of primer sets on detection of the gene encoding biofilm-associated protein (Bap) in Acinetobacter baumannii: in silico and in vitro analysis.

The Acinetobacter baumannii virulence protein Bap is encoded by a large gene and contains both variable sequence and repetitive modules. To date, four primer sets targeting different regions of bap have been designed, but no study has evaluated all these primers simultaneously for detection of bap. Here, we assessed the effect of primer sets Bap I-IV, on detection of bap both in silico and in vitro. Using the primer set Bap II, all 143 tested strains yielded an amplicon corresponding to the bap gene. This primer set showed the highest sensitivity (100, 95% CI: 97·9-100%) compared to the other primer sets. This study demonstrates that primer set Bap II performs with optimal efficiency for detection of the bap gene among different strains. SIGNIFICANCE AND IMPACT OF THE STUDY: This study investigated the effect of nucleotide variation on PCR detection of the bap gene in various Acinetobacter baumannii strains. Since bap is the target gene for many detection assays, this variation can affect the detection efficiency. Here we present a primer set Bap II with optimal detection efficiency amongst 143 different strains, as shown by in silico and in vitro evidence.