• Genomics & Informatics
• /
• v.21 no.3
• /
• pp.42.1-42.23
• /
• 2023

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, one of the most deadly infections in humans. The emergence of multidrug-resistant and extensively drug-resistant Mtb strains presents a global challenge. Mtb has shown resistance to many frontline antibiotics, including rifampicin, kanamycin, isoniazid, and capreomycin. The only licensed vaccine, Bacille Calmette-Guerin, does not efficiently protect against adult pulmonary tuberculosis. Therefore, it is urgently necessary to develop new vaccines to prevent infections caused by these strains. We used a subtractive proteomics approach on 23 virulent Mtb strains and identified a conserved membrane protein (MmpL4, NP_214964.1) as both a potential drug target and vaccine candidate. MmpL4 is a non-homologous essential protein in the host and is involved in the pathogen-specific pathway. Furthermore, MmpL4 shows no homology with anti-targets and has limited homology to human gut microflora, potentially reducing the likelihood of adverse effects and cross-reactivity if therapeutics specific to this protein are developed. Subsequently, we constructed a highly soluble, safe, antigenic, and stable multi-subunit vaccine from the MmpL4 protein using immunoinformatics. Molecular dynamics simulations revealed the stability of the vaccine-bound Tolllike receptor-4 complex on a nanosecond scale, and immune simulations indicated strong primary and secondary immune responses in the host. Therefore, our study identifies a new target that could expedite the design of effective therapeutics, and the designed vaccine should be validated. Future directions include an extensive molecular interaction analysis, in silico cloning, wet-lab experiments, and evaluation and comparison of the designed candidate as both a DNA vaccine and protein vaccine.

• Journal of Pharmacopuncture
• /
• v.27 no.2
• /
• pp.91-100
• /
• 2024

Objectives: Candida albicans is an opportunistic pathogen that occurs as harmless commensals in the intestine, urogenital tract, and skin. It has been influenced by a variety of host conditions and has now evolved as a resistant strain. The aim of this study was thus detect the fluconazole resistant C. albicans from the root caries specimens and to computationally evaluate the interactions of an opaque-phase ABC transporter protein with the Psidium guajava bio-active compounds. Methods: 20 carious scrapings were collected from patients with root caries and processed for the isolation of C. albicans and was screened for fluconazole resistance. Genomic DNA was extracted and molecular characterization of Cdrp1 and Cdrp2 was done by PCR amplification. P. guajava methanolic extract was checked for the antifungal efficacy against the resistant strain of C. albicans. Further in-silico docking involves retrieval of ABC transporter protein and ligand optimization, molinspiration assessment on drug likeness, docking simulations and visualizations. Results: 65% of the samples showed the presence of C.albicans and 2 strains were fluconazole resistant. Crude methanolic extract of P. guajava was found to be promising against the fluconazole resistant strains of C. albicans. In-silico docking analysis showed that Myricetin was a promising candidate with a high docking score and other drug ligand interaction scores. Conclusion: The current study emphasizes that bioactive compounds from Psidium guajava to be a promising candidate for treating candidiasis in fluconazole resistant strains of C. albicans However, further in-vivo studies have to be implemented for the experimental validation of the same in improving the oral health and hygiene.

• Korean Journal of Poultry Science
• /
• v.38 no.2
• /
• pp.155-164
• /
• 2011

The use of antimicrobials will be soon removed due to an increase of occurrence of antibiotic-resistant bacteria or ionophore-resistant Eimeria species in poultry farms and consumers' preference on drug-free chicken meats or eggs. Although dietary antimicrobials contributed to the growth and health of the chickens, we do not fully understand their interrelationship among antimicrobials, gut microbiota, and host immunity in poultry. In this review, we explored the current understanding on the effects of antimicrobials on gut microbiota and immune systems of chickens. Based on the published literatures, it is clear that antibiotics and antibiotic ionophores, when used singly or in combination could influence gut microbiota. However, antimicrobial effect on gut microbiota varied depending on the samples (e.g., gut locations, digesta vs. mucosa) used and among the experiments. It was noted that the digesta vs. the mucosa is the preferred sample with the results of no change, increase, or decrease in gut microbiota community. In future, the mucosa-associated bacteria should be targeted as they are known to closely interact with the host immune system and pathogen control. Although limited, dietary antimicrobials are known to modulate humoral and cell-mediated immunities. Ironically, the evidence is increasing that dietary antimicrobials may play an important role in triggering enteric disease such as gangrenous dermatitis, a devastating disease in poultry industry. Future work should be done to unravel our understanding on the complex interaction of host-pathogen-microbiota-antimicrobials in poultry.

• Safety and Health at Work
• /
• v.3 no.2
• /
• pp.85-91
• /
• 2012

The occupations involved in food animal production have long been recognized to carry significant health risks for workers, with special attention to injuries. However, risk of pathogen exposure in these occupations has been less extensively considered. Pathogens are a food safety issue and are known to be present throughout the food animal production chain. Workers employed at farms and slaughterhouses are at risk of pathogen exposure and bacterial infections. The industrialization of animal farming and the use of antimicrobials in animal feed to promote growth have increased the development of antimicrobial resistance. The changed nature of these pathogens exposes workers in this industry to new strains, thus modifying the risks and health consequences for these workers. These risks are not yet recognized by any work-related health and safety agency in the world.

• Tuberculosis and Respiratory Diseases
• /
• v.44 no.3
• /
• pp.470-478
• /
• 1997

Background : Phagocytosis is probably the first step for mycobacteria to be virulent in host because virulent strains are more readily phagocytosed by macrophage than attenuated strains. According to the traditional concept, multi-drug resistant strains have been regarded as less virulent. However, this concept has been challenged, since recent studies(reported) showed that the degree of virulence and drug-resistance is not related. The purpose of this study is to evaluate whether the phagocytic activity of M.tuberculosis by peripheral blood mononuclear cells(PBMC) is different according to drug-resistance or host factor. To evaluate this, we estimated the difference of phagocytic activity of drug-resistant and drug-sensitive M.tuberculosis and also estimated the phagocytic activity of PBMC from intractable tuberculosis patients and healthy controls. Methods : PBMC from ten intractable tuberculosis patients and twelve healthy control, and three different strains of heat-killed M.tuberculosis, ie, ADS(all drug sensitive), MDR(multi-drug resistant), and ADR(all drug resistant) were used. After incubation of various strains of M.tuberculosis with PBMC, the phagocytic activity was evaluated by estimating proportion of PBMC which have phagocytosed M.tuberculosis. Results : Drug-resistant strains of M.tuberculosis were phagocytosed easily than drug sensitive strains(Percentage of PBMC phagocytosed M.tuberculosis in healthy control : ADS : $32.3{\pm}2.9%$, ADR : $49.6{\pm}3.4%$, p = 0.0022, Percentage of PBMC phagocytosed M.tuberculosis in intractable tuberculosis patients : ADS : $34.9{\pm}3.6%$, ADR : $50.7{\pm}4.5%$, p = 0.0069). However, there was no difference in phagocytic activity of PBMC from healthy control and intractable tuberculosis patients. Conclusion : Drug-resistant strains of M.tuberculosis were phagocytosed easily than drug sensitive strains and host factors does not seems to influence the phagocytosis of M.tuberculosis.

• Microbiology and Biotechnology Letters
• /
• v.47 no.4
• /
• pp.651-661
• /
• 2019

Targeting the pathogen viability using drugs is associated with development of drug resistance due to selective pressure. Hence, there is an increased interest in developing agents that target bacterial virulence. In this study, the inhibitory effect of ciclopirox, an antifungal agent with iron chelation potential, on the microbial virulence factors was evaluated in 26 clinical MDR Pseudomonas aeruginosa isolates collected from Alexandria Main University Hospital, a tertiary hospital in Egypt. Treatment with 9 ㎍/ml ciclopirox inhibited the hemolytic activity in 70% isolates, reduced pyocyanin production, decreased protease secretion in 46% isolates, lowered twitching and swarming motility, and decreased biofilm formation by 1.5- to 4.5-fold. The quantitative real-time PCR analysis revealed that treatment with ciclopirox downregulated the expression levels of alkaline protease (aprA) and pyocyanin (phzA1). Ciclopirox is used to treat hematological malignancies and the systemic administration of ciclopirox is reported to have adequate oral absorption with a satisfactory drug safety profile. It is important to calculate the appropriate clinical dose and therapeutic index to reposition ciclopirox from a topical antifungal agent to a promising virulence-modifying agent agent against P. aeruginosa, a problematic Gram-negative pathogen.

• Korean Journal of Veterinary Service
• /
• v.39 no.3
• /
• pp.175-181
• /
• 2016

Staphylococcus pseudintermedius is an important opportunistic pathogen of dog and cats. Since 2006 there has been a significant emergence of methicillin-resistant S. pseudintermedius (MRSP) mainly due to clonal spread. The aim of this study was to investigated the prevalence of antibiotic resistance and presence of mecA and femA gene in 91 S. pseudintermedius isolates isolated from dogs and cats associated with various clinic infections. Methicillin resistance was confirmed by oxacillin disc diffusion method. MRSP isolate was detected 19 isolates (20.9%). MRSP and methicillin-resistant S. pseudintermedius (MSSP) isolates were highly resistant to penicillin, kanamycin, tetracycline, erythromycin, trimethoprim-sulfamethoxazole, clindamycin, ciprofloxacin, enrofloxacin and choloramphenicol (100~47.3% and 90.3~33.3%, respectively). About 90% of MRSP isolates were multi-drug resistance (resistance to at least five or more antimicrobials), and MSSP isolates was ca 74%. Among the 91 isolates, mecA gene was detected in 25 isolates (27.5%, 19 in MRSP isolates and 6 in MSSP isolates), but none carried the femA gene. Our results indicated MRSA isolates show a strong resistance to antimicrobials commonly used in veterinary medicine. A continuous surveillance and monitoring should be called for to prevent the contamination and spread of MRSP in dogs and cats.

• Journal of Korean Society on Water Environment
• /
• v.28 no.6
• /
• pp.911-916
• /
• 2012

Recently, antibiotic resistant genes (ARGs) in the environment are emerging as pollutants, since these genetic contaminants can eventually be transferred to human pathogens. The aim of this study was to develop the experimental model of antibiotic resistant gene (ARG) plasmid transfer as a function of various environmental conditions. For this purpose, the multi drug resistant plasmid pB10, which is known to be originally isolated from a wastewater treatment plant, was selected as a model transfer plasmid and Escherichia coli $DH5{\alpha}$ containing pB10 was used as a model donor. Pseudomonas aeruginosa, an opportunistic pathogen, was selected as the recipient for the conjugation experiment. When the donor and recipient were exposed to various stressors including antibiotics and heavy metal as a function of the concentrations (10, 100 and, 1000 ppb), statistically increased plasmid transfer rate was observed at a concentration of 10 ppb of tetracycline and sulfamethoxazole compared to control (no antibiotic exposure). Accordingly, the developed experimental ARG model by various stressor is a promising tool for evaluating the dissemination of ARGs by micro-contaminants in aquatic environment.

• Acute and Critical Care
• /
• v.33 no.4
• /
• pp.238-245
• /
• 2018

Background: Infection by multidrug-resistant (MDR) pathogens leads to poor patient outcomes in intensive care units (ICUs). Contact precautions are necessary to reduce the transmission of MDR pathogens. However, the importance of the surrounding environment is not well known. We studied the effects of ICU relocation on MDR respiratory pathogen detection rates and patient outcomes. Methods: Patients admitted to the ICU before and after the relocation were retrospectively analyzed. Baseline patient characteristics, types of respiratory pathogens detected, antibiotics used, and patient outcomes were measured. Results: A total of 463 adult patients admitted to the ICU, 4 months before and after the relocation, were included. Of them, 234 were admitted to the ICU before the relocation and 229 afterward. Baseline characteristics, including age, sex, and underlying comorbidities, did not differ between the two groups. After the relocation, the incidence rate of MDR respiratory pathogen detection decreased from 90.0 to 68.8 cases per 1,000 patient-days, but that difference was statistically insignificant. The use of colistin was significantly reduced from 53.5 days (95% confidence interval [CI], 20.3 to 86.7 days) to 18.7 days (95% CI, 5.6 to 31.7 days). Furthermore, the duration of hospital stay was significantly reduced from a median of 29 days (interquartile range [IQR], 14 to 50 days) to 21 days (IQR, 11 to 39 days). Conclusions: Incidence rates of MDR respiratory pathogen detection were not significantly different before and after ICU relocation. However, ICU relocation could be helpful in reducing the use of antibiotics against MDR pathogens and improving patient outcomes.

• Journal of Yeungnam Medical Science
• /
• v.28 no.2
• /
• pp.133-144
• /
• 2011

Background: Tigecycline (TIG), a new broad-spectrum glycylcycline with anti-multidrug-resistant-(MDR)-pathogen activity, was launched in March 2009 in South Korea, but there are insufficient clinical studies on its use in the country. As such, this study was performed to analyze cases of severe MDR-pathogen-caused infections treated with TIG. Methods: Patients treated with TIG within the period from May 2009 to June 2010 were enrolled in this study. Their clinical and microbiologic data were reviewed retrospectively. Results: Twenty-one patients were treated with TIG for complicated skin and soft-tissue infections (cSSTIs) (42.9%), complicated intra-abdominal infections (cIAIs) (38.1%), or pneumonia (19.1%) caused by MDR pathogens like carbapenem-resistant $Acinetobacter$ $baumannii$ (76.2%), methicillin-resistant $Staphylococcus$ $aureus$ (61.9%), extended-spectrum beta-lactamase-producing $Escherichia$ $coli$ and $Klebsiella$ $pneumoniae$ (38.1%), and penicillin-resistant $Enterococcus$ species (33.3%). Thirteen patients (61.9%) had successful clinical outcomes while five (23.8%) died within 30 days. The rate of clinical success was highest in cSSTI (77.8%), followed by cIAI (50%) and pneumonia (50%), and the mortality rate was highest in pneumonia (50%), followed by cIAI (25%) and cSSTI (11.1%), Conclusion: Tigecycline therapy can be an option for the treatment of severe MDR-pathogen-caused infections in South Korea, Due to its high risk of failure and mortality, however, prudence is required in its clinical use for the treatment of severe infections like nosocomial pneumonia.