Cyclic-di-AMP (c-di-AMP) is a bacterial second messenger that is produced by intracellular bacterial pathogens in mammalian host macrophages. Previous reports have shown that c-di-AMP is recognized by intracellular pattern recognition receptors of the innate immune system and stimulate type I interferon response. Here we report that the response to c-di-AMP includes a post-transcriptional component that is involved in the induction of additional inflammatory cytokines including IL-6, CXCL2, CCL3, and CCL4. Their mRNAs contain AU-rich elements (AREs) in their 3 ′ UTR that promote decay and repress translation. We show that c-di-AMP leads to the phosphorylation of p38 MAPK as well as the induction of the ARE-binding protein TTP, both of which are components of a signaling pathway that modulate the expression of ARE-containing mRNAs at the post-transcriptional level. Pharmacological inhibition of p38 reduces the c-di-AMP-dependent release of induced cytokines, while TTP knockdown increases their release and mRNA stability. C-di-AMP can specifically increase the expression of a nano-Luciferase reporter that contains AREs. We propose a non-canonical intracellular mode of activation of the p38 MAPK pathway with the subsequent enhancement in the expression of inflammatory cytokines. C-di-AMP is widely distributed in bacteria, including infectious intracellular pathogens; hence, understanding of its post-transcriptional gene regulatory effect on the host response may provide novel approaches for therapy.

In transplant recipients, infections are fatal and they can cause considerable morbidity due to constant changes of infection patterns, evolving donor-recipient characteristics, surgical techniques and immunosuppression regimens. The prevalence of resistance to antibiotics among bacteria causes infection in kidney transplant patients (KTPs). This type of infection is caused by a widespread use of antibiotics to prevent and treat infection in those patients. Objectives: The aim of the present study was to determine the incidence of urinary track infections (UTIs) among renal transplant recipients. The study also investigates the antimicrobial susceptibility pattern of causative agents. Materials and Methods: In this study, 200 samples of wound and urine were collected from patients admitted to Zheen international hospital in Erbil city in one year (January of 2019 to January of 2020). Two isolated gram negative (GN) strains were identified by using cultural, morphological, characteristics, and biochemical tests and Vitek 2 system. Results: From the 200 samples, 9 (4.5%) E.coli and K.pneumonia bacteria isolates were taken. Out of 9 (4.5%) of isolates, 4 isolated E.coli species were equal in males and females 4 (44.4%). K.pneumonia was 1 (11.1%) in females, and there was no isolation in males. Our results showed that urine was the major source of bacterial isolates collected comprising 6 were positive. E.coli 5(55.6%) for K. pneumoniae was 1(11.1%), while for wound swab was 3 samples E.coli 3(33.3%) and no K.pneumonia. Our results showed that most isolates of E.coli and K.pneumoniae were highly resistant against the majority of antibiotics, Escherichia coli and K. pneumonia showed 100% resistance against Ampicillin, Amoxicillin and Cloxacillin. The percentage of the resistance of E. coli to Trimethoprim/ Sulfamethoxazole, Azithromycin was high (88.9%). Also, sensitivity was as follows, Amikacin (88.89%), Ertapenem (88.89%), Gentamycin (77.78%), Meropenem (88.89%), Imipenem (88.89%), Tazobactam (77.78%). Extendedspectrum beta-lactamase ESBL production was very common among Ecoli, where out of the 8 (88.9%) E.coli isolates, 4 (44.4%) were producers of ESBL. However, K.pneumonia isolates were not. Conclusions: ESBL producing bacteria increase the rate of morbidity and mortality. This increase entails high healthcare costs. Also, MDR pathogens caused infections are a therapeutic challenge for clinicians and a risk for immuno-compromised patients. There are some antibiotics for the treatment of these infections. These antibiotics can be recommended mostly for non-oral means of administration but have higher risks of side effects.