Tetracycline resistance mediated by tet efflux pumps in clinical isolates of Acinetobacter baumannii

Acinetobacter baumannii is one of the most frequent nosocomial pathogen capable of acquiring resistance to different antimicrobials. The aim of this study was to investigate the activity of tetracycline, doxycycline and minocycline, the prevalence of tet(A) and tet(B) determinants, and the role of efflux pump in tetracycline resistance among the A. baumannii clinical isolates. Susceptibility of 98 A. baumannii isolates to tetracyclines was evaluated by disk diffusion method. The presence of active efflux pump was investigated by determination of the minimum inhibitory concentration (MIC) of tetracycline using the carbonyl cyanide 3-chlorophenylhydrazone (CCCP). Polymerase chain reaction (PCR) was performed to investigate the presence of tet(A) and tet(B) determinants in tetracycline-resistant isolates. The rate of resistance to tetracycline, doxycycline and minocycline was 47.95%, 0%, and 30.61%, respectively. Among the 47 tetracycline-resistant isolates, 29.79% were originated from burned patients and showed MIC ranging from 128-256 µg/mL with both MIC50 and MIC90 values of 256 µg/mL, while 70.21% were from ventilator-associated pneumonia (VAP) patients and had MIC values ranging from 32-1024 µg/mL, with MIC50 and MIC90 of 512 µg/mL and 1024 µg/mL, respectively. The tet(B) gene was found in 61.7% of tetracycline-resistant isolates, while none of the isolates carried the tet(A) gene. CCCP led to 2-128-fold reduction in tetracycline MIC of the tested isolates. The results showed that doxycycline and minocycline are promising agents for the treatment of A. baumannii infections. This study has also revealed the role of efflux activity in the resistance to tetracycline of A. baumannii isolates. The emergence of resistance to these agents is likely due to the spread of clones presenting with a higher prevalence of resistance determinants

Seroprevalence and Sources of Toxoplasmosis among Orang Asli (Indigenous) Communities in Peninsular Malaysia

This study aims to evaluate the current seroprevalence of toxoplasmosis among indigenous communities in Peninsular Malaysia and relate its association with epidemiological data. Overall seroprevalence of Toxoplasma gondii was 37.0% with 31.0% immunoglobulin (Ig) G, 1.8% IgM, and 4.2% seropositivity for both anti- Toxoplasma antibodies. Multivariate analysis showed that age above 12 years (odds ratio [OR] = 2.70, 95% confidence interval [CI] = 1.75–4.04, P < 0.001), using untreated river and mountain water supplies (OR = 1.50, 95% CI = 1.01–2.40, P = 0.050), and close proximity with cats (OR = 1.40, 95% CI = 1.10–1.76, P = 0.010) were factors associated with toxoplasmosis. Given the high seroprevalence of toxoplasmosis among these communities who live in poor socioeconomic conditions, a comprehensive health surveillance program and screening should be initiated among women of childbearing age and pregnant women during the antenatal period for early diagnosis and treatment. The role of domestic cats and environmental contamination with oocyst in soil and water has to be highlighted and addressed in future prevention strategies for these communities

Recombinant Dense Granular Protein (GRA5) for Detection of Human Toxoplasmosis by Western Blot

Toxoplasma gondii infects all warm-blooded animals, including humans, causing serious public health problems and great economic loss for the food industry. Commonly used serological tests require costly and hazardous preparation of whole Toxoplasma lysate antigens from tachyzoites. Here, we have evaluated an alternative method for antigen production, which involved a prokaryotic expression system. Specifically, we expressed T. gondii dense granular protein-5 (GRA5) in Escherichia coli and isolated it by affinity purification. The serodiagnostic potential of the purified recombinant GRA5 (rGRA5) was tested through Western blot analysis against 212 human patient serum samples. We found that rGRA5 protein was 100% specific for analysis of toxoplasmosis-negative human sera. Also, rGRA5 was able to detect acute and chronic T. gondii infections (sensitivities of 46.8% and 61.2%, resp.)

The Garlic Tree of Borneo, Scorodocarpus borneensis (Baill.) Becc. (Olacaceae): Potential Utilization in Pharmaceutical, Nutraceutical, and Functional Cosmetic Industries

Scorodocarpus borneensis (Baill.) Becc. is attracting increased attention as a potential commercial medicinal plant product in Southeast Asia. This review summarizes the current knowledge on the taxonomy, habitat, distribution, medicinal uses, natural products, pharmacology, toxicology, and potential utilization of S. borneesis in the pharmaceutical/nutraceutical/functional cosmetic industries. All data in this review were compiled from Google Scholar, PubMed, Science Direct, Web of Science, ChemSpider, PubChem, and a library search from 1866 to 2022. A total of 33 natural products have been identified, of which 11 were organosulfur compounds. The main organosulfur compound in the seeds is bis-(methylthiomethyl)disulfide, which inhibited the growth of a broad spectrum of bacteria and fungi, T-lymphoblastic leukemia cells, as well as platelet aggregation. Organic extracts evoked anti-microbial, cytotoxic, anti-free radical, and termiticidal effects. S. borneensis and its natural products have important and potentially patentable pharmacological properties. In particular, the seeds have the potential to be used as a source of food preservatives, antiseptics, or termiticides. However, there is a need to establish acute and chronic toxicity, to examine in vivo pharmacological effects and to perform clinical studies

Natural products from medicinal plants in Asia and the Pacific for RNA viruses: Hercules’ fifth labour

Context: The emergence of zoonotic viruses in the last decades culminating with COVID-19 and challenges posed by the resistance of RNA viruses to antiviral drugs requires the development of new antiviral drugs. Objective: This review identifies natural products isolated from Asian and Pacific medicinal plants with in vitro and in vivo antiviral activity towards RNA viruses and analyses their distribution, molecular weights, solubility and modes of action. Materials and methods: All data in this review was compiled from Google Scholar, PubMed, Science Direct, Web of Science, ChemSpider, PubChem and library search from 1961 to 2022. Results: Out of about 350 molecules identified, 43 phenolics, 31 alkaloids, and 28 terpenes were very strongly active against at least one type of RNA virus. These natural products are mainly planar and amphiphilic, with a molecular mass between 200 and 400 g/mol and target viral genome replication. Hydroxytyrosol, silvestrol, lycorine, tylophorine and 12-O-tetradecanoylphorbol 13-acetate with IC50 below 0.01 mg/mL and selectivity index (S.I.) above 100 have the potential to be used for the development of anti-RNA virus leads. Discussion and conclusions: The medicinal plants of Asia and the Pacific are a rich source of natural products with the potential to be developed as lead for the treatment of RNA viral infections

Increased detection of Plasmodium knowlesi in Sandakan division, Sabah as revealed by PlasmoNex

Background: Plasmodium knowlesi is a simian malaria parasite that is widespread in humans in Malaysian Borneo. However, little is known about the incidence and distribution of this parasite in the Sandakan division, Malaysian Borneo. Therefore, the aim of the present epidemiological study was to investigate the incidence and distribution of P. knowlesi as well as other Plasmodium species in this division based on a most recent developed hexaplex PCR system (PlasmoNex™). Methods: A total of 189 whole blood samples were collected from Telupid Health Clinic, Sabah, Malaysia, from 2008 to 2011. All patients who participated in the study were microscopically malaria positive before recruitment. Complete demographic details and haematological profiles were obtained from 85 patients (13 females and 72 males). Identification of Plasmodium species was conducted using PlasmoNex™ targeting the 18S ssu rRNA gene. Results: A total of 178 samples were positive for Plasmodium species by using PlasmoNex™. Plasmodium falciparum was identified in 68 samples (38.2%) followed by 64 cases (36.0%) of Plasmodium vivax, 42 (23.6%) cases of P. knowlesi, two (1.1%) cases of Plasmodium malariae and two (1.1%) mixed-species infections (i e, P. vivax/ P. falciparum). Thirty-five PlasmoNex™ positive P. knowlesi samples were misdiagnosed as P. malariae by microscopy. Plasmodium knowlesi was detected in all four districts of Sandakan division with the highest incidence in the Kinabatangan district. Thrombocytopaenia and anaemia showed to be the most frequent malaria-associated haematological complications in this study. Conclusions: The discovery of P. knowlesi in Sandakan division showed that prospective studies on the epidemiological risk factors and transmission dynamics of P. knowlesi in these areas are crucial in order to develop strategies for effective malaria control. The availability of advanced diagnostic tool PlasmoNex™ enhanced the accuracy and accelerated the speed in the diagnosis of malari