Recent Updates on Bacterial Secondary Metabolites to Overcome Antibiotic Resistance in Gram-Negative Superbugs: Encouragement or Discontinuation?

2022 ◽  
pp. 385-418
Author(s):  
Manoj Jangra ◽  
Parminder Kaur ◽  
Rushikesh Tambat ◽  
Vrushali Raka ◽  
Nisha Mahey ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Secondary Metabolites ◽  
Gram Negative

scholarly journals Chemical Composition and Antimicrobial Activity of Two Sri Lankan Lichens, Parmotrema rampoddense, and Parmotrema tinctorum against Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureus

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Polwatta Samaraweera Arachchige Ishara Shiromi ◽  
Ruwani Punyakanthi Hewawasam ◽  
Rankoth Gedara Udeni Jayalal ◽  
Hasanga Rathnayake ◽  
Weerasinghe Mudiyanselage Dilip Gaya Bandara Wijayaratne ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Chemical Composition ◽  
Secondary Metabolites ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Ethanol Extract ◽  
Aqueous Extracts ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Parmotrema Tinctorum

Introduction. Medicinal utility of lichens is ascribed to the presence of various secondary metabolites of low molecular weight and they have been used in traditional medicine including Ayurveda in the treatment of wounds and skin disorders. Despite the urgent need to effectively address the antibiotic resistance worldwide, the discovery of new antibacterial drugs has declined in the recent past. This emphasizes the increasing importance of investigating and developing new classes of antibiotics that can withstand antibiotic resistance. Aims of the study. The present study was conducted to investigate the chemical composition and the antibacterial activity of hexane, ethanol, and aqueous extracts of Parmotrema rampoddense and Parmotrema tinctorum, two lichens collected from Belihuloya, Sri Lanka, against Gram-negative and Gram-positive bacteria including twenty clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). Materials and methods. Phytochemical analysis, thin layer chromatography (TLC), and Gas Chromatography Mass Spectrometry (GC-MS) were performed to determine the chemical composition of the two lichens. Hexane, ethanol, and aqueous extracts of both lichens were tested against clinical isolate of Gram-negative and Gram-positive bacteria including twenty clinical isolates of MRSA. Bacterial susceptibility was tested using a disc diffusion assay. Minimum inhibitory concentration (MIC) was determined by a broth microdilution method. Vancomycin was used as the positive control. Results. Alectorialic acid, atranorin, atraric acid, orcinol, and O-orsellinaldehyde were among the secondary metabolites identified by the TLC and GC-MS analysis. None of the lichen extracts were active against Gram-negative bacteria but both lichens showed a concentration-dependent activity against methicillin-sensitive Staphylococcus aureus (MSSA) and MRSA. Ethanol extract of P. rampoddense showed the highest activity against MSSA with the MIC, 0.0192 mg/ml, but all MRSA isolates investigated showed MIC between 0.096 and 2.4 mg/ml for the same extract. Conclusion. Both lichens, P. rampoddense and P. tinctorum, represent potentially important sources of future antimicrobial drugs. Further investigation on the ethanol extract of P. rampoddense will enable us to determine the most active phytoconstituents responsible for the activity, their mechanism of action against bacterial pathogens, and also their cytotoxicity against normal cells.

scholarly journals Myxobacteria as a Source of New Bioactive Compounds: A Perspective Study

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1265
Author(s):  
Mudasir Ahmad Bhat ◽  
Awdhesh Kumar Mishra ◽  
Mujtaba Aamir Bhat ◽  
Mohammad Iqbal Banday ◽  
Ommer Bashir ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Secondary Metabolites ◽  
Bioactive Compounds ◽  
Polyketide Synthases ◽  
Fruiting Bodies ◽  
Natural Sources ◽  
Gram Negative ◽  
Wide Range ◽  
New Antibiotics ◽  
Derivatives Of

Myxobacteria are unicellular, Gram-negative, soil-dwelling, gliding bacteria that belong to class δ-proteobacteria and order Myxococcales. They grow and proliferate by transverse fission under normal conditions, but form fruiting bodies which contain myxospores during unfavorable conditions. In view of the escalating problem of antibiotic resistance among disease-causing pathogens, it becomes mandatory to search for new antibiotics effective against such pathogens from natural sources. Among the different approaches, Myxobacteria, having a rich armor of secondary metabolites, preferably derivatives of polyketide synthases (PKSs) along with non-ribosomal peptide synthases (NRPSs) and their hybrids, are currently being explored as producers of new antibiotics. The Myxobacterial species are functionally characterized to assess their ability to produce antibacterial, antifungal, anticancer, antimalarial, immunosuppressive, cytotoxic and antioxidative bioactive compounds. In our study, we have found their compounds to be effective against a wide range of pathogens associated with the concurrence of different infectious diseases.

In vitro antibacterial and antibiotic-potentiation activities of five edible plant extracts and mode of action against several MDR Gram-negative phenotypes

2020 ◽  
Vol 4 (1) ◽  
pp. 1-14
Author(s):  
Carine M.N. Ngaffo ◽  
Simplice B. Tankeo ◽  
Michel-Gael F. Guefack ◽  
Brice E. N. Wamba ◽  
Paul Nayim ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Bioactive Compounds ◽  
Plant Extracts ◽  
Theobroma Cacao ◽  
Efflux Pumps ◽  
Phoenix Dactylifera ◽  
Food Plants ◽  
Proton Pumps ◽  
Gram Negative ◽  
E Coli

Abstract Background: Bacterial infections involving the multidrug resistant (MDR) strains are among the top leading causes of death throughout the world. Healthcare system across the globe has been suffering from an extra-ordinary burden in terms of looking for the new and more potent antimicrobial compounds. The aim of the present study was to determine the antibacterial activity of some Cameroonian edible plants (Garcinia lucida bark, Phoenix dactylifera pericarps, Theobroma cacao pod, Solanum macrocarpon leaves and Termitomyces titanicus whole plant) and their antibiotics-potentiation effects against some MDR Gram-negative bacteria phenotypes expressing efflux pumps (Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa and Providencia stuartii strains). Methods: The antibacterial activities of plant extract alone and in combination with usual antibiotics were carried out using the micro-dilution method. The effects of the most active plant extract (Garcinia lucida bark) on H+-ATPase-mediated proton pumps and on bacterial growth kinetic were performed using experimental protocols, while qualitative reference methods were used to highligh the major groups of secondary metabolites present in the extracts. Results: Qualitative phytochemical screening of plant extracts indicated that all analysed secondary metabolites were present in Theobroma cacao and Termitomyces titanicus while one (saponins) of them was absent in Garcinia lucida and Solanum macrocarpon. Only three of them (polyphenols, flavonoids and saponins) were detected in Phoenix dactylifera. Antibacterial essays showed that G. lucida was the most active plant as it inhibited the growth of all studied bacteria with strong activity (MIC<100 µg/mL) against E. coli ATCC8739, significant activity (100≤MIC≤512 µg/mL) against 80% of bacteria and moderate activity (512<MIC≤2048 µg/mL) against E. coli AG100A and E. aerogenes (EA289 and CM64). It was followed by T. cacao and S. macrocarpon extracts which exhibited an antibacterial potential against 95% and 80% of bacterial strains, respectively. These three extracts exhibited a bactericidal effect on a few bacteria. Extracts from T. titanicus and P. dactylifera were less active as they moderately (512<MIC≤2048 µg/mL) inhibited the growth of 35% and 10% of bacteria. All extracts selectively potentiated the activities of all antibiotics with improvement activity factors (IAF) ranging from 2 to 256. G. lucida, T. cacao and S. macrocarpon potentiated the activities of 100%, 89% and 67% of antibiotics respectively against more than 70%, suggesting that they contain bioactive compounds which could be considered as efflux pumps inhibitors. Whereas T. titanicus and P. dactylifera improved the activities of almost 40% and 20% of antibiotics, respectively. This increase of activities also characterizes synergistic effects between antibiotics and these bioactive compounds. G. lucida extract at all tested concentrations, strongly inhibited the growth of bacterial strain E. coli ATCC8739 and exhibited an inhibitory effect on this bacterial H+-ATPase-mediated proton pumps increasing the pH of the medium. Conclusion: The overall results indicated that food plants among which G. lucida, T. cacao and S. macrocarpon could have a benefit interest in combatting resistant types of bacteria. Keywords: Food plants; infectious diseases; MDR bacteria; efflux pumps; antibiotics; secondary metabolites.

Genome sequence of Novosphingobium malaysiense strain MUSC 273T, novel alpha-proteobacterium isolated from intertidal soil

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Hooi-Leng Ser ◽  
Wai-Fong Yin ◽  
Kok-Gan Chan ◽  
Nurul-Syakima Ab Mutalib ◽  
Learn-Han Lee
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Genome Sequence ◽  
Catalase Activity ◽  
Gene Clusters ◽  
Rrna Genes ◽  
Gram Negative ◽  
Genomic Features

Novosphingobium malaysiense strain MUSC 273T is a recently identified Gram-negative, aerobic alpha-proteobacterium. The strain was isolated from intertidal soil with strong catalase activity. The genome sequence comprises 5,027,021 bp, with 50 tRNA and 3 rRNA genes. Further analysis identified presence of secondary metabolite gene clusters within genome of MUSC 273T. Knowledge of the genomic features of the strain may allow further biotechnological exploitation, particularly for production of secondary metabolites as well as production of industrially important enzymes

Extended Spectrum Beta Lactamase (ESBL), bla TEM,bla SHVand bla CTX-M,resistance genes in Community and Healthcare Associated Gram Negative Bacteria from Osun State, Nigeria

2020 ◽  
Vol 20 ◽  
Author(s):  
Ganiyat Shitta ◽  
Olufunmilola Makanjuola ◽  
Olusolabomi Adefioye ◽  
Olugbenga Adekunle Olowe
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Gram Negative Bacteria ◽  
Beta Lactamase ◽  
Multiple Antibiotic Resistance ◽  
Esbl Production ◽  
Gram Negative ◽  
Extended Spectrum Beta Lactamase ◽  
Healthcare Associated ◽  
Esbl Producers

Background: Extended Spectrum Beta Lactamase (ESBL) production in gram negative bacteria confers multiple antibiotic resistance, adversely affecting antimicrobial therapy in infected individuals. ESBLs result from mutations in β-lactamases encoded mainly by the bla TEM,bla SHVand bla CTX-Mgenes. The prevalence of ESBL producing bacteria has been on the increase globally especially its upsurge among isolates from community-acquired infections. Aim: To determine ESBL prevalence and identify ESBL genes among clinical isolates in Osun State, Nigeria. Material and Methods: A cross-sectional study was carried out from August 2016 –July 2017 in Osun State, Nigeria. Three hundred and sixty Gram negative bacteria recovered from clinical samples obtained from both community and healthcare associated infections were tested. They included147 Escherichia coli(40.8%), 116 Klebsiella spp(32.2%), 44 Pseudomo-nas aeruginosa(12.2%) and23 Proteus vulgaris (6.4%) isolates. Others were Acinetobacter baumannii, Serratia rubidae, Citrobacter spp, Enterobacter spp and Salmonella typhi. Disk diffusion antibiotic susceptibility testing was carried out, isolates were screened for ESBL production and confirmed using standard laboratory procedures. ESBLs resistance genes were identified by Polymerase Chain Reaction (PCR). Results: All isolates demonstrated multiple antibiotic resistance. Resistance to ampicillin, amoxicillin with clavulanate and erythromycin was 100%, whereas resistance to Imipenem was very low (5.0%). : Overall prevalence of ESBL producers was 41.4% with Klebsiellaspp as the highest ESBL producing Enterobacteriacaea. ESBL producers were more prevalent among the hospital pathogens than community pathogens, 58% vs 29.5% (p=0.003). ESBL genes were detected in all ESBL producers with the blaCTX-Mgene predominating (47.0%) followed by blaTEM(30.9%) and blaSHVgene was the least, 22.1%. The blaCTX-Mgene was also the most prevalent in the healthcare pathogens (62%) but it accounted for only 25% in those of community origin. Conclusion: A high prevalence of ESBL producing gram negative organisms occurs both in healthcare and in the community in our environment with the CTX-M variant predominating. Efforts to control spread of these pathogens should be addressed.

scholarly journals Correlation between the Antibiotic Resistance Genes and Susceptibility to Antibiotics among the Carbapenem-Resistant Gram-Negative Pathogens

Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 255
Author(s):  
Salma M. Abdelaziz ◽  
Khaled M. Aboshanab ◽  
Ibrahim S. Yahia ◽  
Mahmoud A. Yassien ◽  
Nadia A. Hassouna
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Efflux Pump ◽  
Antibiotic Resistance Genes ◽  
Multiple Drug ◽  
P Value ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Gram Negative ◽  
Carbapenem Resistant

In this study, the correlation between the antibiotic resistance genes and antibiotic susceptibility among the carbapenem-resistant Gram-negative pathogens (CRGNPs) recovered from patients diagnosed with acute pneumonia in Egypt was found. A total of 194 isolates including Klebsiella pneumoniae (89; 46%), Escherichia coli (47; 24%) and Pseudomonas aeruginosa (58; 30%) were recovered. Of these, 34 (18%) isolates were multiple drug resistant (MDR) and carbapenem resistant. For the K. pneumoniae MDR isolates (n = 22), blaNDM (14; 64%) was the most prevalent carbapenemase, followed by blaOXA-48 (11; 50%) and blaVIM (4; 18%). A significant association (p value < 0.05) was observed between the multidrug efflux pump (AcrA) and resistance to β-lactams and the aminoglycoside acetyl transferase gene (aac-6’-Ib) gene and resistance to ciprofloxacin, azithromycin and β-lactams (except for aztreonam). For P. aeruginosa, a significant association was noticed between the presence of the blaSHV gene and the multidrug efflux pump (MexA) and resistance to fluoroquinolones, amikacin, tobramycin, co-trimoxazole and β-lactams and between the aac-6’-Ib gene and resistance to aminoglycosides. All P. aeruginosa isolates (100%) harbored the MexAB-OprM multidrug efflux pump while 86% of the K. pneumoniae isolates harbored the AcrAB-TolC pump. Our results are of great medical importance for the guidance of healthcare practitioners for effective antibiotic prescription.

scholarly journals Utilization of Vector Autoregressive and Linear Transfer Models to Follow Up the Antibiotic Resistance Spiral in Gram-negative Bacteria From Cephalosporin Consumption to Colistin Resistance

2018 ◽  
Vol 69 (8) ◽  
pp. 1410-1421 ◽  
Author(s):  
Hajnalka Tóth ◽  
Adina Fésűs ◽  
Orsolya Kungler-Gorácz ◽  
Bence Balázs ◽  
László Majoros ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Carbapenem Resistance ◽  
Gram Negative Bacteria ◽  
Vicious Cycle ◽  
Var Models ◽  
Gram Negative ◽  
Vector Autoregressive ◽  
E Coli ◽  
Cephalosporin Resistance ◽  
Klebsiella Spp

Abstract Background Increasing antibiotic resistance may reciprocally affect consumption and lead to use of broader-spectrum alternatives; a vicious cycle that may gradually limit therapeutic options. Our aim in this study was to demonstrate this vicious cycle in gram-negative bacteria and show the utility of vector autoregressive (VAR) models for time-series analysis in explanatory and dependent roles simultaneously. Methods Monthly drug consumption data in defined daily doses per 100 bed-days and incidence densities of gram-negative bacteria (Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, and Acinetobacter baumannii) resistant to cephalosporins or to carbapenems were analyzed using VAR models. These were compared to linear transfer models used earlier. Results In case of all gram-negative bacteria, cephalosporin consumption led to increasing cephalosporin resistance, which provoked carbapenem use and consequent carbapenem resistance and finally increased colistin consumption, exemplifying the vicious cycle. Different species were involved in different ways. For example, cephalosporin-resistant Klebsiella spp. provoked carbapenem use less than E. coli, and the association between carbapenem resistance of P. aeruginosa and colistin use was weaker than that of A. baumannii. Colistin use led to decreased carbapenem use and decreased carbapenem resistance of P. aeruginosa but not of A. baumannii. Conclusions VAR models allow analysis of consumption and resistance series in a bidirectional manner. The reconstructed resistance spiral involved cephalosporin use augmenting cephalosporin resistance primarily in E. coli. This led to increased carbapenem use, provoking spread of carbapenem-resistant A. baumannii and consequent colistin use. Emergence of panresistance is fueled by such antibiotic-resistance spirals.

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