Explore the vast range of titles available.

Staphylococcus aureus is an opportunistic pathogen and the leading cause of a wide range of severe clinical infections. The range of diseases reflects the diversity of virulence factors produced by this pathogen. To establish an infection in the host, S. aureus expresses an inclusive set of virulence factors such as toxins, enzymes, adhesins, and other surface proteins that allow the pathogen to survive under extreme conditions and are essential for the bacteria’s ability to spread through tissues. Expression and secretion of this array of toxins and enzymes are tightly controlled by a number of regulatory systems. S. aureus is also notorious for its ability to resist the arsenal of currently available antibiotics and dissemination of various multidrug-resistant S. aureus clones limits therapeutic options for a S. aureus infection. Recently, the development of anti-virulence therapeutics that neutralize S. aureus toxins or block the pathways that regulate toxin production has shown potential in thwarting the bacteria’s acquisition of antibiotic resistance. In this review, we provide insights into the regulation of S. aureus toxin production and potential anti-virulence strategies that target S. aureus toxins.

Dysbiosis of the gut microbiome has been associated with the pathogenesis of colorectal cancer (CRC). We profiled the microbiome of gut mucosal tissues from 18 CRC patients and 18 non-CRC controls of the UKM Medical Centre (UKMMC), Kuala Lumpur, Malaysia. The results were then validated using a species-specific quantitative PCR in 40 CRC and 20 non-CRC tissues samples from the UMBI-UKMMC Biobank. Parvimonas micra , Fusobacterium nucleatum , Peptostreptococcus stomatis and Akkermansia muciniphila were found to be over-represented in our CRC patients compared to non-CRC controls. These four bacteria markers distinguished CRC from controls (AUROC = 0.925) in our validation cohort. We identified bacteria species significantly associated (cut-off value of > 5 fold abundance) with various CRC demographics such as ethnicity, gender and CRC staging; however, due to small sample size of the discovery cohort, these results could not be further verified in our validation cohort. In summary, Parvimonas micra , Fusobacterium nucleatum , Peptostreptococcus stomatis and Akkermansia muciniphila were enriched in our local CRC patients. Nevertheless, the roles of these bacteria in CRC initiation and progression remains to be investigated.

Cancer is a global health problem associated with genetics and unhealthy lifestyles. Increasingly, pathogenic infections have also been identified as contributors to human cancer initiation and progression. Most pathogens (bacteria, viruses, fungi, and parasites) associated with human cancers are categorized as Group I human carcinogens by the International Agency for Research on Cancer, IARC. These pathogens cause carcinogenesis via three known mechanisms: persistent infection that cause inflammation and DNA damage, initiation of oncogene expression, and immunosuppression activity of the host. In this review, we discuss the carcinogenesis mechanism of ten pathogens, their implications, and some future considerations for better management of the disease. The pathogens and cancers described are Helicobacter pylori (gastric cancer), Epstein-Barr virus (gastric cancer and lymphoma), Hepatitis B and C viruses (liver cancer), Aspergillus spp. (liver cancer), Opisthorchis viverrine (bile duct cancer), Clonorchis sinensis (bile duct cancer), Fusobacterium nucleatum (colorectal cancer), Schistosoma haematobium (bladder cancer); Human Papillomavirus (cervical cancer), and Kaposi’s Sarcoma Herpes Virus (Kaposi’s sarcoma).

The resistance of ESBLs-producing Kp to various groups of antibiotics commonly used against infections they caused had become a global threat and required urgent attention. This study assessed the extended spectrum beta-lactamases (ESBLs)-producing Klebsiella pneumoniae isolates in terms of their genomic resistance. An analytical profile index (API) 20E kit was used to confirm a total of 100 clinical isolates of ESBL Klebsiella pneumoniae . The disc diffusion method was used to perform the antimicrobial susceptibility testing (AST), which was followed by the phenotypic detection of ESBLs. Six profiled representative ESBL positive strains were subjected to whole genome sequencing (WGS), multilocus sequence typing (MLST), and phylogenetic tree construction using the sequence data. The study showed that 46(46%) of the 100 isolates were positive for ESBL production and antibiotic susceptibility testing revealed significant resistance to β-lactam antibiotics including monobactam especially ampicillin/sulbactam (40%), cephalosporin groups (cefuroxime, cefotaxime, and ceftriaxone) stood at 51%, 49% and 48% respectively and aztreonam with 49%. The WGS analysis of the representative strains revealed genes encoding resistance to aminoglycoside (S trA4 , StrB1 , aac(3’)-IIa , aac(6’)-1b , aac(6’)1b-cr-1 , aadA16 , aph(3’)-VIa and aadA15 ), trimethoprim ( dfrA14 and dfrA27 ), sulphonamide ( sul1_11 , sul2_2 and sul2_3 ), quinolone ( QnrB40-1 , QnrB10 , QnrS2 , OqxA and OqxB ), tetracycline (tet(A)_4), fosfomycin ( fosA3 , floR2 and fosA7 ), macrolid ( mph(A)_1 ), rifampicin ( ARR-3 ), β-lactam ( blaCTX-M-15_23 , blaCTX-M-55 , blaSHV-1_22 , blaSHV11_18 , blaSHV-11 , blaSHV-1_1.1 , blaSHV-11_3 , blaSHV-11_19 , blaTEM-1_1 , blaTEM-1_5 , blaOXA-51_10 , blaOXA-30_1 , blaNDM-1 , blaLEN6 , blaLEN8 and blaLEN21 were detected. The MLST analysis revealed two novel sequence types of representative strains (2 with ST NF * and 12 with ST NF) and four other heterogeneous STs which include ST394, ST985, ST17 and ST11 while the phylogenetic tree of the strains showed closed clonal relationship and lineages with other reference isolates. In conclusion, the study’s results showed a high prevalence of ESBL-producing Kp in the study area, and the representative strains’ genomic contents demonstrated that ESBL-producing Kp in a clinical setting could serve as a reservoir for resistance genes and be the source of genetic transfer to other bacterial species. As a result, ongoing surveillance is required to monitor this endemic situation to prevent an epidemiological outbreak of K. pneumoniae- carrying ESBL.

Genome inversions are ubiquitous in organisms ranging from prokaryotes to eukaryotes. Typical examples can be identified by comparing the genomes of two or more closely related organisms, where genome inversion footprints are clearly visible. Although the evolutionary implications of this phenomenon are huge, little is known about the function and biological meaning of this process. Here, we report our findings on a bacterium that generates a reversible, large-scale inversion of its chromosome (about half of its total genome) at high frequencies of up to once every four generations. This inversion switches on or off bacterial phenotypes, including colony morphology, antibiotic susceptibility, hemolytic activity, and expression of dozens of genes. Quantitative measurements and mathematical analyses indicate that this reversible switching is stochastic but self-organized so as to maintain two forms of stable cell populations (i.e., small colony variant, normal colony variant) as a bet-hedging strategy. Thus, this heritable and reversible genome fluctuation seems to govern the bacterial life cycle; it has a profound impact on the course and outcomes of bacterial infections.

Bacterial culture and biochemical testing (CBtest) have been the cornerstone of pathogen identification in the diagnostic microbiology laboratory. With the advent of Sanger sequencing and later, next-generation sequencing, 16S rRNA next-generation sequencing (16SNGS) has been proposed to be a plausible platform for this purpose. Nevertheless, usage of the 16SNGS platform has both advantages and limitations. In addition, transition from the traditional methods of CBtest to 16SNGS requires procurement of costly equipment, timely and sustainable maintenance of these platforms, specific facility infrastructure and technical expertise. All these factors pose a challenge for middle-income countries, more so for countries in the lower middle-income range. In this review, we describe the basis for CBtest and 16SNGS, and discuss the limitations, challenges, advantages and future potential of using 16SNGS for bacterial pathogen identification in diagnostic microbiology laboratories of middle-income countries.

The gut microbiota Parvimonas micra has been found to be enriched in gut mucosal tissues and fecal samples of colorectal cancer (CRC) patients compared with non-CRC controls. In the present study, we investigated the tumorigenic potential of P. micra and its regulatory pathways in CRC using HT-29, a low-grade CRC intestinal epithelial cell. For every P. micra-HT-29 interaction assay, HT-29 was co-cultured anaerobically with P. micra at an MOI of 100:1 (bacteria: cells) for 2 h. We found that P. micra increased HT-29 cell proliferation by 38.45% (P=0.008), with the highest wound healing rate at 24 h post-infection (P=0.02). In addition, inflammatory marker expression (IL-5, IL-8, CCL20, and CSF2) was also significantly induced. Shotgun proteomics profiling analysis revealed that P. micra affects the protein expression of HT-29 (157 up-regulated and 214 down-regulated proteins). Up-regulation of PSMB4 protein and its neighbouring subunits revealed association of the ubiquitin–proteasome pathway (UPP) in CRC carcinogenesis; whereas down-regulation of CUL1, YWHAH, and MCM3 signified cell cycle dysregulation. Moreover, 22 clinically relevant epithelial–mesenchymal transition (EMT)-markers were expressed in HT-29 infected with P. micra. Overall, the present study elucidated exacerbated oncogenic properties of P. micra in HT-29 via aberrant cell proliferation, enhanced wound healing, inflammation, up-regulation of UPPs, and activation of EMT pathways.

Early bacterial infection (BI) identification in resource-limiting Emergency Departments (ED) is challenging, especially in low- and middle-income counties (LMIC). Misdiagnosis predisposes to antibiotic overuse and propagates antimicrobial resistance. This study evaluates new emerging biomarkers, secretory phospholipase A2 group IIA (sPLA2-IIA) and compares with other biomarkers on their performance characteristic of BI detection in Malaysia, an LMIC. A prospective cohort study was conducted involving 151 consecutive patients admitted to the ED. A single measurement was taken upon patient arrival in ED and was analysed for serum levels of sPLA2-IIA, high-sensitive C-reactive protein (CRP), procalcitonin (PCT), neutrophil percentage (N%), and lactate. All biomarkers’ performance was compared for the outcomes using area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity. The performance of sPLA2-IIA (AUROC 0.93 [95% CI: 0.89–0.97]; Sn 80% [95% CI: 72–87]; Sp 94% [95% CI: 81–89]) was the highest among all. It was comparable with high-sensitive CRP (AUROC 0.93 [95% CI: 0.88–0.97]; Sn 75% [95% CI: 66–83]; Sp 91 [95% CI: 77–98]) but had a higher Sn and Sp. The sPLA2-IIA was also found superior to N%, PCT, and lactate. This finding suggested sPLA2-IIA was recommended biomarkers for BI detection in LMIC.

Introduction The alteration of the gut microbiome in the gut-kidney axis has been associated with a pro-inflammatory state and chronic kidney disease (CKD). A small-scaled Italian study has shown an association between the gut microbiome and Immunoglobulin A Nephropathy (IgAN). However, there is no data on gut microbiota in IgAN in the Asian population. This study compares the gut microbial abundance and diversity between healthy volunteers and Malaysian IgAN cohort. Methods A comparative cross-sectional study was conducted involving biopsy-proven IgAN patients in clinical remission with matched controls in a Malaysian tertiary centre. Demographic data, routine blood and urine results were recorded. Stool samples were collected and their DNA was extracted by 16S rRNA gene sequencing to profile their gut microbiota. Results Thirty-six IgAN patients (13 male; 23 female) with the mean age of 45.5 ± 13.4 years and median estimated glomerular filtration rate (eGFR) of 79.0 (62.1–92.2) mls/min/1.73m 2 with median remission of 7 years were analysed and compared with 12 healthy controls (4 male; 8 female) with the mean age of 46.5 ± 13.5 years and eGFR of 86.5 (74.2–93.7) mls/min/1.73m 2 . Other demographic and laboratory parameters such as gender, ethnicity, body mass index (BMI), haemoglobin, serum urea and serum albumin were comparable between the two groups. There were no significant differences seen in the Operational Taxonomic Unit (OTU) and alpha diversity (Shannon index) between IgAN and healthy controls. Alpha diversity increased with increasing CKD stage ( p  = 0.025). Firmicutes/Bacteroidetes (F/B) ratio was low in both IgAN and healthy cohort. Fusobacteria phylum was significantly increased ( p  = 0.005) whereas Euryarchaoeota phylum was reduced ( p  = 0.016) in the IgAN group as compared to the control cohort. Conclusion Although we found no differences in OTU and alpha diversity between IgAN in remission and control cohort, there were some differences between the two groups at phylum level.

Introduction: Since the dawn of the new millennium, Candida species have been increasingly implicated as a cause of both healthcare-associated as well as opportunistic yeast infections, due to the widespread use of indwelling medical devices, total parenteral nutrition, systemic corticosteroids, cytotoxic chemotherapy, and broad-spectrum antibiotics. Candida tropicalis is a pathogenic Candida species associated with considerable morbidity, mortality, and drug resistance issues on a global scale. Methodology: We report a case of a 43-year-old man who was admitted to our hospital for further management of severe coronavirus disease 2019 (COVID-19) pneumonia. During his stay in the ward, he received systemic corticosteroids for a total duration of 32 days. A broad-spectrum antibiotic (piperacillin-tazobactam) was also given due to copious amounts of tracheostomy secretions. Results: The patient’s fever recurred following an afebrile interval of 11 days, and C. tropicalis was cultured from his blood. The yeast was highly resistant to fluconazole and voriconazole but remained susceptible to echinocandins. Unfortunately, the patient was unable to receive any echinocandin and eventually succumbed to candidemia. Conclusions: Multilocus sequence typing was used to characterize C. tropicalis as a novel diploid sequence type (i.e., 1515) that has not been previously reported.