The cGAS-STING Pathway in Bacterial Infection and Bacterial Immunity

Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) (cGAMP) synthase (cGAS), along with the adaptor stimulator of interferon genes (STING), are crucial components of the innate immune system, and their study has become a research hotspot in recent years. Many biochemical and structural studies that have collectively elucidated the mechanism of activation of the cGAS-STING pathway with atomic resolution have provided insights into the roles of the cGAS-STING pathway in innate immunity and clues to the origin and evolution of the modern cGAS-STING signaling pathway. The cGAS-STING pathway has been identified to protect the host against viral infection. After detecting viral dsDNA, cGAS synthesizes a second messenger to activate STING, eliciting antiviral immune responses by promoting the expression of interferons (IFNs) and hundreds of IFN-stimulated genes (ISGs). Recently, the cGAS-STING pathway has also been found to be involved in response to bacterial infections, including bacterial pneumonia, melioidosis, tuberculosis, and sepsis. However, compared with its functions in viral infection, the cGAS-STING signaling pathway in bacterial infection is more complex and diverse since the protective and detrimental effects of type I IFN (IFN-I) on the host depend on the bacterial species and infection mode. Besides, STING activation can also affect infection prognosis through other mechanisms in different bacterial infections, independent of the IFN-I response. Interestingly, the core protein components of the mammalian cGAS-STING signaling pathway have been found in the bacterial defense system, suggesting that this widespread signaling pathway may have originated in bacteria. Here, we review recent findings related to the structures of major molecules involved in the cGAS-STING pathway and the effects of the cGAS-STING pathway in various bacterial infections and bacterial immunity, which may pave the way for the development of new antibacterial drugs that specifically kill bacteria without harmful effects on the host.

Baseline procalcitonin as a predictor of bacterial infection and clinical outcomes in COVID-19: A case-control study

Purpose Coronavirus disease-2019 (COVID-19) is associated with a wide spectrum of clinical symptoms including acute respiratory failure. Biomarkers that can predict outcomes in patients with COVID-19 can assist with patient management. The aim of this study is to evaluate whether procalcitonin (PCT) can predict clinical outcome and bacterial superinfection in patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Methods Adult patients diagnosed with SARS-CoV-2 by nasopharyngeal PCR who were admitted to a tertiary care center in Boston, MA with SARS-CoV-2 infection between March 17 and April 30, 2020 with a baseline PCT value were studied. Patients who were presumed positive for SARS-CoV-2, who lacked PCT levels, or who had a positive urinalysis with negative cultures were excluded. Demographics, clinical and laboratory data were extracted from the electronic medical records. Results 324 patient charts were reviewed and grouped by clinical and microbiologic outcomes by day 28. Baseline PCT levels were significantly higher for patients who were treated for true bacteremia (p = 0.0005) and bacterial pneumonia (p = 0.00077) compared with the non-bacterial infection group. Baseline PCT positively correlated with the NIAID ordinal scale and survival over time. When compared to other inflammatory biomarkers, PCT showed superiority in predicting bacteremia. Conclusions Baseline PCT levels are associated with outcome and bacterial superinfection in patients hospitalized with SARS-CoV-2.

Causes of post treatment apical periodontitis

Endodontic treatment approaches aim to achieve proper treatment and prevention of apical periodontitis to enhance the oral health status and enhance the prognosis of affected teeth. However, many complications can develop secondary to endodontic treatment. The management of post-treatment apical periodontitis might be challenging to clinicians, and the prognosis is usually lower than that of primary apical periodontitis. Therefore, identifying the potential etiology and intervening against them might be ideal for these cases. The present literature review discusses the commonest causes reported in the literature to predispose to the development of post-treatment apical periodontitis. Most of the various investigations in the literature indicate that post-treatment apical periodontitis is usually caused by either extraradicular or intraradicular infections, like primary apical periodontitis. However, it should be noted that some studies also reported that technical or procedural errors might predispose to the pathogenesis of the condition. However, it has been reported that the presence of associated bacterial infection conditions this.

Effect of Caring of Critically Sick Patients with COVID-19 Pneumonia at Undesignated ICU Wards on Secondary Infections

<b><i>Introduction:</i></b> COVID-19 has caused high rates of mortality. During pandemic peak, a significant number of patients were admitted to undesignated ICU areas before transferring to designated ICU, owing to unavailability of ICU beds. We aimed to record the effect of care of critically sick patients with COVID-19 on prevalence of secondary bacterial infection. <b><i>Methods:</i></b> We retrospectively studied all critically ill patients with COVID-19 pneumonia meeting ICU admission criteria who were admitted to Dubai hospital between January 1, 2020, and June 30, 2020. All the patients who transferred to wards other than designated ICU constitute category as cases. All patients who directly admitted to the designated ICU ward from emergency department constitute controls. The demographics, clinical parameters, and treatment profile of these patients were recorded and compared. Prevalence of secondary bacterial infection was calculated. <b><i>Results:</i></b> Patients with COVID-19 had high prevalence of secondary bacterial infection. Patients who stayed at undesignated ICU wards had higher occurrence of inpatient fever, hypoxemia, and they were more likely to be sedated and paralyzed than patients who stayed in designated ICU wards. Multiple logistic regression analysis showed care outside designated ICU ward does not predict increase in secondary nonviral microbial infections. <b><i>Conclusion:</i></b> Care of patients at undesignated ICU wards prior to admission to designated ICU does not impact prevalence of secondary bacterial infection.

Distinction between Antimicrobial Resistance and Putative Virulence Genes Characterization in Plesiomonas shigelloides Isolated from Different Sources

Plesiomonas shigelloides are gram-negative, thermotolerant, motile, and pleomorphic microorganisms that are only distantly related to those of the Enterobacteriaceae and Vibrionaceae families. One of the most common sources of P. shigelloides contamination is human stool, but it may also be found in a wide range of other animals, plants, and aquatic habitats. Antimicrobial resistance in P. shigelloides from seawater and shellfish was investigated, and pathogenicity involved genes were characterized as part of this study. Out of 384 samples of shellfish, 5.7% included P. shigelloides. The presence of P. shigelloides was also discovered in 5% of the seawater sampled. The antimicrobial resistance of 23 P. shigelloides isolates derived from those samples was investigated. All isolates were sensitive to nalidixic acid, carbenicillin, cephalothin, erythromycin, kanamycin, tetracycline, and ciprofloxacin in the study. Several strains isolated from diseased shellfish were tested for virulence in shellfish by intraperitoneal injections. The LD50 values ranged from 12 × 108 to 3 × 1012 cfu/shellfish. When looking for possible virulence factors that may play a significant role in bacterial infection in the current study, we found that all of these genes were present in these strains. These include genes such as elastase, lipase, flagellin, enterotoxin, and DNases. According to these findings, shellfish may serve as a reservoir for multi-resistant P. shigelloides and help spread virulence genes across the environment.