Mining of plant-derived antimicrobials is the major focus at current to counter antibiotic resistance. This study was conducted to characterize the antimicrobial activity and mode of action of linalyl anthranilate (LNA) against carbapenemase-producing Klebsiella pneumoniae (KPC-KP). LNA alone exhibited bactericidal activity at 2.5% (V/V), and in combination with meropenem (MPM) at 1.25% (V/V). Comparative proteomic analysis showed a significant reduction in the number of cytoplasmic and membrane proteins, indicating membrane damage in LNA-treated KPC-KP cells. Up-regulation of oxidative stress regulator proteins and down-regulation of oxidative stress-sensitive proteins indicated oxidative stress. Zeta potential measurement and outer membrane permeability assay revealed that LNA increases both bacterial surface charge and membrane permeability. Ethidium bromide influx/efflux assay showed increased uptake of ethidium bromide in LNA-treated cells, inferring membrane damage. Furthermore, intracellular leakage of nucleic acid and proteins was detected upon LNA treatment. Scanning and transmission electron microscopies again revealed the breakage of bacterial membrane and loss of intracellular materials. LNA was found to induce oxidative stress by generating reactive oxygen species (ROS) that initiate lipid peroxidation and damage the bacterial membrane. In conclusion, LNA generates ROS, initiates lipid peroxidation, and damages the bacterial membrane, resulting in intracellular leakage and eventually killing the KPC-KP cells.
Antibiotics have revolutionised medicine in the last century and enabled the prevention of bacterial infections that were previously deemed untreatable. However, in parallel, bacteria have increasingly developed resistance to antibiotics through various mechanisms. When resistant bacteria find their way into terrestrial and aquatic environments, animal and human exposures increase, e.g., via polluted soil, food, and water, and health risks multiply. Understanding the fate and transport of antibiotic resistant bacteria (ARB) and the transfer mechanisms of antibiotic resistance genes (ARGs) in aquatic environments is critical for evaluating and mitigating the risks of resistant-induced infections. The conceptual understanding of sources and pathways of antibiotics, ARB, and ARGs from society to the water environments is essential for setting the scene and developing an appropriate framework for modelling. Various factors and processes associated with hydrology, ecology, and climate change can significantly affect the fate and transport of ARB and ARGs in natural environments. This article reviews current knowledge, research gaps, and priorities for developing water quality models to assess the fate and transport of ARB and ARGs. The paper also provides inputs on future research needs, especially the need for new predictive models to guide risk assessment on AR transmission and spread in aquatic environments.
Matched MeSH terms: Drug Resistance, Microbial/genetics
Multidrug microbial resistance poses major challenges to the management of infection, particularly with the paucity of new drugs with activity against these bacteria. Since the turn of this century a few new antibiotics have been licensed, including linezolid, daptomycin and tigecycline. This supplement reports data presented at the 13th International Congress of Infectious Diseases held in Kuala Lumpur in June 2008. Dr R. Isturiz reviews the data on global resistance trends and the potential impact on empirical therapy; Dr J.-H. Song reviews new agents on the antimicrobial horizon; and the final paper in the supplement, by Dr L.R. Peterson, reviews the role of tigecycline in the management of complicated intra-abdominal and skin and soft tissue infections.
Vibrio species isolated from four different sampling stations in the west coast of Peninsular Malaysia were screened for their antimicrobial resistance and plasmid profiles. A total of 138 isolates belonging to 15 different species were identified. Vibrio campbellii, V. parahaemolyticus, V. harveyi, and V. tubiashii were found to predominance species at all stations. High incidence of erythromycin, ampicillin, and mecillinam resistance was observed among the Vibrio isolates. In contrast, resistance against aztreonam, cefepime, streptomycin, sulfamethoxazole, and sulfonamides was low. All the Vibrio isolates in this study were found to be susceptible to imipenem, norfloxacin, ofloxacin, chloramphenicol, trimethoprim/sulfamethoxazole, and oxytetracycline. Ninety-five percent of the Vibrio isolates were resistant to one or more different classes of antibiotic, and 20 different resistance antibiograms were identified. Thirty-two distinct plasmid profiles with molecular weight ranging from 2.2 to 24.8 kb were detected among the resistance isolates. This study showed that multidrug-resistant Vibrio spp. were common in the aquatic environments of west coast of Peninsular Malaysia.
Matched MeSH terms: Drug Resistance, Microbial/genetics*
As the causative agent of foodborne related illness, Vibrio species causes a huge impact on the public health and management. Vibrio species is often associated with seafood as the latter plays a role as a vehicle to transmit bacterial infections. Hence, antibiotics are used not to promote growth but rather to prevent and treat bacterial infections. The extensive use of antibiotics in the aquaculture industry and environment has led to the emerging of antibiotic resistant strains. This phenomenon has triggered an alarming public health concern due to the increase number of pathogenic Vibrio strains that are resistant to clinically used antibiotics and is found in the environment. Antibiotic resistance and the genes location in the strains can be detected through plasmid curing assay. The results derived from plasmid curing assay is fast, cost effective, sufficient in providing insights, and influence the antibiotic management policies in the aquaculture industry. This presentation aims in discussing and providing insights on various curing agents in Vibrio species. To our best of knowledge, this is a first review written discussing on plasmid curing in Vibrio species.
Vibrio vulnificus is a Gram negative, rod shaped bacterium that belongs to the family Vibrionaceae. It is a deadly, opportunistic human pathogen which is responsible for the majority of seafood-associated deaths worldwide. V. vulnificus infection can be fatal as it may cause severe wound infections potentially requiring amputation or lead to sepsis in susceptible individuals. Treatment is increasingly challenging as V. vulnificus has begun to develop resistance against certain antibiotics due to their indiscriminate use. This article aims to provide insight into the antibiotic resistance of V. vulnificus in different parts of the world as well as an overall review of its clinical manifestations, treatment, and prevention. Understanding the organism's antibiotic resistance profile is vital in order to select appropriate treatment and initiate appropriate prevention measures to treat and control V. vulnificus infections, which should eventually help lower the mortality rate associated with this pathogen worldwide.
Methicillin-resistant Staphylococcus aureus (MRSA) pose a significant health threat as they tend to cause severe infections in vulnerable populations and are difficult to treat due to a limited range of effective antibiotics and also their ability to form biofilm. These organisms were once limited to hospital acquired infections but are now widely present in the community and even in animals. Furthermore, these organisms are constantly evolving to develop resistance to more antibiotics. This results in a need for new clinically useful antibiotics and one potential source are the Streptomyces which have already been the source of several anti-MRSA drugs including vancomycin. There remain large numbers of Streptomyces potentially undiscovered in underexplored regions such as mangrove, deserts, marine, and freshwater environments as well as endophytes. Organisms from these regions also face significant challenges to survival which often result in the production of novel bioactive compounds, several of which have already shown promise in drug development. We review the various mechanisms of antibiotic resistance in MRSA and all the known compounds isolated from Streptomyces with anti-MRSA activity with a focus on those from underexplored regions. The isolation of the full array of compounds Streptomyces are potentially capable of producing in the laboratory has proven a challenge, we also review techniques that have been used to overcome this obstacle including genetic cluster analysis. Additionally, we review the in vivo work done thus far with promising compounds of Streptomyces origin as well as the animal models that could be used for this work.
In this study, the differences on the physico-chemical parameters, lignocellulose degradation, dynamic succession of microbial community, gene expression of carbohydrate-active enzymes and antibiotics resistance genes were compared during composting systems of bagasse pith/pig manure (BP) and manioc waste/pig manure (MW). The results revealed that biodegradation rates of organic matter, cellulose, hemicellulose and lignin (29.14%, 17.53%,45.36% and 36.48%) in BP were higher than those (15.59%, 16.74%, 41.23% and 29.77%) in MW. In addition, the relative abundance of Bacillus, Luteimonas, Clostridium, Pseudomonas, Streptomyces and expression of genes encoding carbohydrate- active enzymes in BP were higher than those in MW based on metagenomics sequencing. During composting, antibiotics and antibiotic resistance genes were substantially reduced, but the removal efficiency was divergent in the both samples. Taken together, metagenomics analysis was a potential method for evaluating lignocellulose's biodegradation process and determining the elimination of antibiotic and antibiotic resistance genes from different composting sources of biomass.
Matched MeSH terms: Drug Resistance, Microbial/drug effects
Gene therapy and vaccines are rapidly developing field in which recombinant nucleic acids are introduced in mammalian cells for enhancement, restoration, initiation or silencing biochemical function. Beside simplicity in manipulation and rapid manufacture process, plasmid DNA-based vaccines have inherent features that make them promising vaccine candidates in a variety of diseases. This present review focuses on the safety concern of the genetic elements of plasmid such as propagation and expression units as well as their host genome for the production of recombinant plasmid DNA. The highlighted issues will be beneficial in characterizing and manufacturing plasmid DNA for save clinical use. Manipulation of regulatory units of plasmid will have impact towards addressing the safety concerns raised in human vaccine applications. The gene revolution with plasmid DNA by alteration of their plasmid and production host genetics will be promising for safe delivery and obtaining efficient outcomes.
Matched MeSH terms: Drug Resistance, Microbial/genetics
Acute pharyngitis (AP) is a common reason for private primary care consultations, thus providing an avenue for widespread antibiotic intake among the community. However, there is limited data on the antibiotic prescription appropriateness and resistance information in the Malaysian private primary care setting, therefore, this study aimed to investigate the prevalence of isolated viruses and bacteria, antibiotic resistance patterns, antibiotic prescription patterns and appropriateness by general practitioners (GPs) and factors affecting antibiotic resistance and antibiotic prescription patterns. To investigate, a cross-sectional study was conducted among 205 patients presenting with AP symptoms at private primary care clinics in central Malaysia from 3rd January 2016 to 30th November 2016. Throat swabs were collected from 205 AP patients for two purposes: (i) the detection of four common respiratory viruses associated with AP via reverse-transcription real-time PCR (qRT-PCR); and (ii) bacterial identification using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). Bacterial isolates were then subjected to antibiotic susceptibility screening and McIsaac scoring was calculated post-prescription based on GP selection of criteria. Generalized estimating equations analysis with multiple logistic regression was conducted to identify factors associated with presence of virus and antibiotic prescription. The results showed that 95.1% (195/205) of patients had at least one of the four viruses, with rhinovirus (88.5%) being the most prevalent, followed by adenovirus (74.9%), influenza A virus (4.6%) and enterovirus (2.1%). A total of 862 non-repetitive colonies were isolated from the culture of throat swabs from 205 patients who were positive for bacteria. From a total of 22 genera, Streptococcus constitutes the most prevalent bacteria genus (40.9%), followed by Neisseria (20%), Rothia (13.0%), Staphylococcus (11%) and Klebsiella (4.9%). Only 5 patients carried group A beta-hemolytic streptococci (GABHS). We also report the presence of vancomycin-resistant S. aureus or VRSA (n = 9, 10.1%) among which one isolate is a multidrug-resistant methicillin-resistant S. aureus (MDR-MRSA), while 54.1% (n = 111) were found to carry at least one antibiotic-resistant bacteria species. Application of the McIsaac scoring system indicated that 87.8% (n = 180) of patients should not be prescribed antibiotics as the majority of AP patients in this study had viral pharyngitis. The antibiotic prescription appropriateness by applying post-prescription McIsaac scoring was able to rule out GABHS pharyngitis in this sample with a GABHS culture-positive sensitivity of 40% (n = 2/5) and specificity of 90% (180/200). In conclusion, antibiotic-resistant throat isolates and over-prescription of antibiotics were observed and McIsaac scoring system is effective in guiding GPs to determine occurrences of viral pharyngitis to reduce unnecessary antibiotic prescription.
A prospective study was carried out at the University Hospital, Kuala Lumpur to determine the cervical carriage rate of Ureaplasma urealyticum and Mycoplasma hominis among healthy pregnant women at delivery and the incidence of nasopharyngeal colonisation among their infants.
The discovery of antibiotics had been one of the most significant events in the history of medicine. Antibiotics had saved countless number of lives and had contributed significantly to the health of mankind.The emergence of resistance is however a major threat to the continued usefulness of antibiotics. There are now strains of bacteria which are resistant to virtually all available antibiotics and these strains are increasingly being encountered in clinical practice. The development of new agents had not kept pace with resistance and it is unlikely that there will be major breakthroughs in the near future. The world needs to conserve and prolong the useful lives of the existing agents. This can only be achieved through good antibiotic stewardship programmes. As antibiotic resistance is a global threat all major stakeholders have to work together to meet this challenge.
Four hundred methicillin-resistant Staphylococcus aureus strains (MRSA) from different geographical areas in Malaysia were tested for mupirocin susceptibility using minimum inhibitory concentration (MIC) determination. The majority of these strains (98.75%) were susceptible to mupirocin with MICs of < or = 4 mg/l. Fifty-percent of these strains had MICs of 0.125 mg/l or less while 90% of the strains had MICs of 1 mg/l or less. Mupirocin resistance was detected in five strains (1.25%) and one of these (0.25%) had an MIC of 64 mg/l and the other four strains (1%), high-level resistance with MICs > 512 mg/l. Even though the rate of mupirocin resistance in MRSA is still low in Malaysia, its presence calls for a strict policy on mupirocin usage in Malaysian hospitals.
Development of new biocides has dominated human responses to evolution of antibiotic and pesticide resistance. Increasing and uniform biocide use, the spread of resistance genes, and the lack of new classes of compounds indicate the importance of navigating toward more sustainable coevolutionary dynamics between human culture and species that evolve resistance. To inform this challenge, we introduce the concept of coevolutionary governance and propose three priorities for its implementation: (i) new norms and mental models for lowering use, (ii) diversifying practices to reduce directional selection, and (iii) investment in collective action institutions to govern connectivity. We highlight the availability of solutions that facilitate broader sustainable development, which for antibiotic resistance include improved sanitation and hygiene, strong health systems, and decreased meat consumption.