Antimicrobial resistance is the rising global health issue that should not be ignored. This problem needs to be addressed and professionally handled since it is starting to threaten global health, which eventually could lead to disaster. Extended spectrum beta lactamase (ESBL)-producing bacteria were found threatening lives, since most antibiotics were found to not be effective in treating patients with infections caused by those bacteria. ESBL-producing Escherichia coli and Klebsiella pneumoniae are the two most reported bacteria in causing the bacteremia and nosocomial infections worldwide. In this article, the prevalence of ESBL-producing E. coli and K. pneumoniae in causing blood stream and urinary tract infections in Indonesia were compared to the neighboring countries based on the global antimicrobial resistance surveillance system performed worldwide by World Health Organization (WHO). In this article, the prevalence of ESBL-producing E. coli and K. pneumoniae in Indonesia and its neighboring countries were assayed and compared in order to evaluate the antimicrobial resistances. By comparing the prevalence data to the neighboring countries, some insightful evidence and information was served to support improved health in Indonesia. Some hurdles and strategies in combating the antimicrobial resistances were further discussed. Eventually, an alternate solution to overcome the antimicrobial drug resistance should be well-provided, studied and implemented globally.

Background: The marine environment is the main source of research on natural products in the future. In addition, marine microorganisms have been identified as a natural source capable of developing new antibiotic compounds, including controlling urinary tract infections caused by Escherichia coli ESBL. Purpose: This study aims to isolate, select, and test the potential of brown macroalgae endophytic fungi (Phaeophyceae) collected from the coastal waters of Sanur, Bali Province. Methods: Three types of brown algae were collected from Sanur Beach and their endophytic fungi were isolated using PDA media. Antibacterial activity was determined by measuring the inhibition zone and determining the inhibition category. The selected isolates were cultured and the phytochemical profile was determined qualitatively. In addition, molecular identification using the Internal Transcribed Spacer (ITS) primer set and comparison with the GenBank (NCBI) database were carried out in this study. Results: The results showed that 10 isolates were successfully isolated from three types of brown macroalgae. It was found that isolates T1, S1, and P3 had the highest inhibition in the very strong category. There were variations in mycelial weight, pH value, and inhibition shown by the culture filtrate of the three endophytic fungal isolates against Escherichia coli ESBL. Isolate S1 had the highest phytochemical profile, namely alkaloids, triterpenoids, saponins, and phenolics. The three endophytic fungal isolates showed isolate T1 (Phlebiopsis magnicystidiata) (MT5617191), isolate P3 (Neurospora crassa strain RT3M) (MT1028551), and isolate S1 (Peniophora sp.) (MH2680421). Conclusion: The results of this study provide initial information regarding the potential of bioprospecting brown macroalgal endophytic fungi as a source of new antibiotics against Escherichia coli ESBL.

Klebsiella pneumoniae is one of abundant normal flora in human, but also well-studied as an opportunistic pathogen due to its ability to form biofilm. Biofilm could be formed by biofilm-forming bacteria as its survival method. Valid example for biofilm-associated medical issue is catheter-related diseases, such as urinary tract infection (UTI). In order to form the biofilm, bacteria utilize the fimbriae in order to form the attachment of bacterial cell and surface of medical equipments. Klebsiella pneumoniae has two types of fimbriae, type I and type III, which play big role in regulating its biofilm formation. We previously found that the expression of type III fimbriae and biofilm formation in K. pneumoniae strain STU1 were tightly regulated by cAMP-CRP pathway, and significantly increased by the overexpression of EtcABC, the component of bacterial phosphoenolpyruvate (PEP):carbohydrate phosphotransferase systems (PTS). Interestingly, by RT-qPCR and Western Blotting, we found that the expression of EtcA in STU1 (the homologue of KPN00353 in K. pneumoniae strain MGH78578) was reduced significantly by high glucose. The reduction of EtcA which was predicted to have role as an EIIA in PTS, significantly reduced the expression of MrkA, the main protein for type III fimbriae assembly and formation. We therefore took K. pneumoniae isolates isolated from Tzu Chi hospital in Hualien, Taiwan to follow the observation we found in STU1 and found the same pattern that the higher the concentration of glucose added in the bacterial culture medium, the less the expression of EtcA and MrkA. In diabetic mellitus patients, K. pneumoniae was often to be the causing agents of pyogenic liver abscess (PLA). From this point of view, we found interesting scenario that probably could be the mechanism of K. pneumoniae infection in diabetic mellitus patients. Our in vitro data strongly suggested that high glucose levels negatively affected the type III fimbriae expression and biofilm formation in K. pneumoniae STU1 and clinical isolates. Further study is indeed worth to be done for unraveling the unknown molecular mechanisms of Klebsiella biofilm formation and infections in certain type of patient conditions.

Non-alcoholic fatty liver disease (NAFLD) is a condition marked by excessive fat accumulation in the liver and poses a significant health challenge. The leaves of Blumea balsamifera and Sargassum aquifolium have been reported to have anti-atherogenic effects. This study aims to determine the effectiveness of B. balsamifera extract (BBLE) and S. aquifolium extract (SAE) in preventing and treating liver fat accumulation in Wistar rats induced by a high-cholesterol diet through the expression of the AMP-activated protein kinase (AMPK)/ Sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor γ (PPARγ) pathway, and the leptin receptor. The experimental design of this study is laboratory-based, involving, 20 Wistar rats were fed a high-cholesterol diet over a period of 21 days. The rats were divided into four groups for the evaluation of BBLE and SAE effect: negative control (P0): induced with a high-cholesterol diet + distilled water, positive control (P1): induced with a high-cholesterol diet + simvastatin, P2: induced with a high-cholesterol diet + 4 mg/kg/bw BBLE, and P3: induced with a high-cholesterol diet + 4 mg/kg/bw BBLE and 4 mg/kg/bw SAE. The treatment duration extended over three months. Immunohistochemical analyses were performed on liver tissues to measure AMPK, SIRT1, PPARγ, and leptin receptor expression. The results indicated that leptin expression was lower in the BBLE+SAE group compared to the simvastatin group, and differences were significant between the BBLE and BBLE+SAE groups. No significant differences were noted in AMPK, SIRT1, and PPARγ expression between the simvastatin and BBLE+SAE groups (p≥0.05). In conclusion, BBLE and SAE effectively reduce liver lipid accumulation and enhance fat metabolism in hypercholesterolemic rats.

Letter for the article Anti-Diarrheal Activities of Hydromethanolic Crude Extract and Solvent Fractions of Acacia seyal (Fabaceae) Roots in Mice