scholarly journals Antibiotic resistance modifying ability of phytoextracts in anthrax biological agent Bacillus anthracis and emerging superbugs: a review of synergistic mechanisms

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Mackingsley Kushan Dassanayake ◽  
Teng-Jin Khoo ◽  
Jia An
Keyword(s):  
Drug Resistance ◽  
Antibiotic Resistance ◽  
Bacillus Anthracis ◽  
Pathogenic Bacteria ◽  
Inhibitory Concentration ◽  
Epigallocatechin Gallate ◽  
Resistance Mechanisms ◽  
Synergistic Activity ◽  
Bacterial Drug Resistance

Abstract Background and objectives The chemotherapeutic management of infections has become challenging due to the global emergence of antibiotic resistant pathogenic bacteria. The recent expansion of studies on plant-derived natural products has lead to the discovery of a plethora of phytochemicals with the potential to combat bacterial drug resistance via various mechanisms of action. This review paper summarizes the primary antibiotic resistance mechanisms of bacteria and also discusses the antibiotic-potentiating ability of phytoextracts and various classes of isolated phytochemicals in reversing antibiotic resistance in anthrax agent Bacillus anthracis and emerging superbug bacteria. Methods Growth inhibitory indices and fractional inhibitory concentration index were applied to evaluate the in vitro synergistic activity of phytoextract-antibiotic combinations in general. Findings A number of studies have indicated that plant-derived natural compounds are capable of significantly reducing the minimum inhibitory concentration of standard antibiotics by altering drug-resistance mechanisms of B. anthracis and other superbug infection causing bacteria. Phytochemical compounds allicin, oleanolic acid, epigallocatechin gallate and curcumin and Jatropha curcas extracts were exceptional synergistic potentiators of various standard antibiotics. Conclusion Considering these facts, phytochemicals represents a valuable and novel source of bioactive compounds with potent antibiotic synergism to modulate bacterial drug-resistance.

scholarly journals Sorting out the Superbugs: Potential of Sortase A Inhibitors among Other Antimicrobial Strategies to Tackle the Problem of Antibiotic Resistance

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 164 ◽  
Author(s):  
Nikita Zrelovs ◽  
Viktorija Kurbatska ◽  
Zhanna Rudevica ◽  
Ainars Leonchiks ◽  
Davids Fridmanis
Keyword(s):  
Cell Wall ◽  
Antibiotic Resistance ◽  
Pathogenic Bacteria ◽  
Resistance Mechanisms ◽  
Surface Proteins ◽  
Sortase A ◽  
Inhibitory Compounds ◽  
Alternative Means ◽  
Alternative Approaches ◽  
Conventional Antibiotics

Rapid spread of antibiotic resistance throughout the kingdom bacteria is inevitably bringing humanity towards the “post-antibiotic” era. The emergence of so-called “superbugs”—pathogen strains that develop resistance to multiple conventional antibiotics—is urging researchers around the globe to work on the development or perfecting of alternative means of tackling the pathogenic bacteria infections. Although various conceptually different approaches are being considered, each comes with its advantages and drawbacks. While drug-resistant pathogens are undoubtedly represented by both Gram(+) and Gram(−) bacteria, possible target spectrum across the proposed alternative approaches of tackling them is variable. Numerous anti-virulence strategies aimed at reducing the pathogenicity of target bacteria rather than eliminating them are being considered among such alternative approaches. Sortase A (SrtA) is a membrane-associated cysteine protease that catalyzes a cell wall sorting reaction by which surface proteins, including virulence factors, are anchored to the bacterial cell wall of Gram(+) bacteria. Although SrtA inhibition seems perspective among the Gram-positive pathogen-targeted antivirulence strategies, it still remains less popular than other alternatives. A decrease in virulence due to inactivation of SrtA activity has been extensively studied in Staphylococcus aureus, but it has also been demonstrated in other Gram(+) species. In this manuscript, results of past studies on the discovery of novel SrtA inhibitory compounds and evaluation of their potency were summarized and commented on. Here, we discussed the rationale behind the inhibition of SrtA, raised some concerns on the comparability of the results from different studies, and touched upon the possible resistance mechanisms as a response to implementation of such therapy in practice. The goal of this article is to encourage further studies of SrtA inhibitory compounds.

scholarly journals Antibacterial Compounds from Mushrooms: A Lead to Fight ESKAPEE Pathogenic Bacteria?

Planta Medica ◽  
2020 ◽  
Author(s):  
Violette Hamers ◽  
Clément Huguet ◽  
Mélanie Bourjot ◽  
Aurélie Urbain
Keyword(s):  
Antibiotic Resistance ◽  
Global Health ◽  
Pathogenic Bacteria ◽  
Resistance Mechanisms ◽  
Pathogenic Microorganisms ◽  
Bacterial Strains ◽  
Antibacterial Compounds ◽  
New Antibiotics ◽  
Hospital Stays ◽  
Antibacterial Potential

AbstractInfectious diseases are among the greatest threats to global health in the 21st century, and one critical concern is due to antibiotic resistance developed by an increasing number of bacterial strains. New resistance mechanisms are emerging with many infections becoming more and more difficult if not impossible to treat. This growing phenomenon not only is associated with increased mortality but also with longer hospital stays and higher medical costs. For these reasons, there is an urgent need to find new antibiotics targeting pathogenic microorganisms such as ESKAPEE bacteria. Most of currently approved antibiotics are derived from microorganisms, but higher fungi could constitute an alternative and remarkable reservoir of anti-infectious compounds. For instance, pleuromutilins constitute the first class of antibiotics derived from mushrooms. However, macromycetes still represent a largely unexplored source. Publications reporting the antibacterial potential of mushroom extracts are emerging, but few purified compounds have been evaluated for their bioactivity on pathogenic bacterial strains. Therefore, the aim of this review is to compile up-to-date data about natural products isolated from fruiting body fungi, which significantly inhibit the growth of ESKAPEE pathogenic bacteria. When available, data regarding modes of action and cytotoxicity, mandatory when considering a possible drug development, have been discussed in order to highlight the most promising compounds.

scholarly journals Assessment of the Drug Susceptibility of Plasmodium falciparum Clinical Isolates from Africa by Using a Plasmodium Lactate Dehydrogenase Immunodetection Assay and an Inhibitory Maximum Effect Model for Precise Measurement of the 50-Percent Inhibitory Concentration

2006 ◽  
Vol 50 (10) ◽  
pp. 3343-3349 ◽  
Author(s):  
Halima Kaddouri ◽  
Serge Nakache ◽  
Sandrine Houzé ◽  
France Mentré ◽  
Jacques Le Bras
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Lactate Dehydrogenase ◽  
Active Metabolite ◽  
Inhibitory Concentration ◽  
Drug Susceptibility ◽  
Maximum Effect ◽  
Malaria Parasites ◽  
Effect Model

ABSTRACT The extension of drug resistance among malaria-causing Plasmodium falciparum parasites in Africa necessitates implementation of new combined therapeutic strategies. Drug susceptibility phenotyping requires precise measurements. Until recently, schizont maturation and isotopic in vitro assays were the only methods available, but their use was limited by technical constraints. This explains the revived interest in the development of replacement methods, such as the Plasmodium lactate dehydrogenase (pLDH) immunodetection assay. We evaluated a commercially controlled pLDH enzyme-linked immunosorbent assay (ELISA; the ELISA-Malaria antigen test; DiaMed AG, Cressier s/Morat, Switzerland) to assess drug susceptibility in a standard in vitro assay using fairly basic laboratory equipment to study the in vitro resistance of malaria parasites to major antimalarials. Five Plasmodium falciparum clones and 121 clinical African isolates collected during 2003 and 2004 were studied by the pLDH ELISA and the [8-3H]hypoxanthine isotopic assay as a reference with four antimalarials. Nonlinear regression with a maximum effect model was used to estimate the 50% inhibitory concentration (IC50) and its confidence intervals. The two methods were observed to have similar reproducibilities, but the pLDH ELISA demonstrated a higher sensitivity. The high correlation (r = 0.98) and the high phenotypic agreement (κ = 0.88) between the two methods allowed comparison by determination of the IC50s. Recently collected Plasmodium falciparum African isolates were tested by pLDH ELISA and showed drug resistance or decreased susceptibilities of 62% to chloroquine and 11.5% to the active metabolite of amodiaquine. No decreased susceptibility to lumefantrine or the active metabolite of artemisinin was detected. The availability of this simple and highly sensitive pLDH immunodetection assay will provide an easier method for drug susceptibility testing of malaria parasites.

scholarly journals EVALUATION OF ANTIBACTERIAL RESISTANCE OF BIOFILM FORMS OF AVIAN SALMONELLA GALLINARUM TO FLUOROQUINOLONES

2018 ◽  
Author(s):  
Kumar Kamashi ◽  
Mr. Honnegowda ◽  
Mayanna Asha ◽  
Chandrakala Ms.
Keyword(s):  
Pathogenic Bacteria ◽  
Inhibitory Concentration ◽  
Minimum Bactericidal Concentration ◽  
Bacterial Biofilms ◽  
Dilution Method ◽  
Post Inoculation ◽  
Antibacterial Resistance ◽  
Salmonella Gallinarum ◽  
Broth Dilution

Antimicrobial resistance is a growing concern worldwide. The indiscriminate use of antibiotics for a period of time has led to the emergence of antibiotic resistance in pathogenic bacteria. The present study was designed to evaluate the antibacterial efficacy of fluoroquinolone drugs, ciprofloxacin, enrofloxacin, moxifloxacin, sparfloxacin, norfloxacin, pefloxacin and ofloxacin against avian Salmonella gallinarum bacterial biofilms. The study parameters, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and biofilm elimination concentration (BEC) were determined on days 1, 3, 7, 10, 14 and 20 post inoculation for the planktonic (free) and biofilm cells of S. gallinarum by macro broth dilution method. The MIC and MBC values determined on days 1, 3, 7, 10, 14 and 20 for each of the fluoroquinolone drugs against the planktonic and biofilm forms of avian S. gallinarum were found to be non-significant. BEC values determined against the biofilm forms of S. gallinarum during the study period were found to be non-significant among the tested fluoroquinolones. The results of the present study demonstrated that fluoroquinolone drugs were effective in vitro against both the planktonic and biofilm forms of avian S. gallinarum.

Phytochemical Screening, Antibacterial and Synergistic activity of Dittrichia Viscosa Extracts against Multi-Resistant Pathogenic Bacteria

2019 ◽  
Vol 2 (1) ◽  
pp. 01-06
Author(s):  
Rhazi Fouzia
Keyword(s):  
Antibacterial Activity ◽  
Pathogenic Bacteria ◽  
Antibacterial Effect ◽  
Synergistic Activity ◽  
Phytochemical Screening ◽  
Bacterial Strains ◽  
Dittrichia Viscosa ◽  
Study Results ◽  
Ethanolic Extracts

Study contextual: Faced with the global problem of antimicrobial resistance, and the use of traditional medicine for the research of antibacterial biomolecules. Aim: our work focused on the valorization of a medicinal plant Dittrichia viscosa which has many therapeutic and culinary virtues worldwide. Methods: To do this, a phytochemical screening of the leafy stems of the plant is carried out according to a set of physicochemical reactions, as well as an in vitro evaluation of the antibacterial activity, of the aqueous and ethanolic extracts against multi-resistant bacterial strains, by microdilution technique on microplates. An evaluation of the synergistic interaction between extracts and weakened antibiotics against pathogenic bacteria was also highlighted in this study. Results: The tests revealed the richness of Dittrichia viscosa species by tannins, flavonoids, saponosides, sterols and triterpenes. As for the antibacterial effect, the MICs range from 0.858±0.29 to 66.66 ± 0.00 mg / ml and the MBCs from 4.300 ± 1.01 to 11.610 ± 2.31 mg / ml is an interesting antibacterial activity. Regarding the combination of extracts with antibiotics tested, it revealed a synergistic action inducing an amplification of the antibacterial power of Penicillin, Imipenem and Erythromycin with a rate that reaches 471%. Conclusion: The results of this study show that the aqueous and ethanolic extracts of Dittrichia viscosa have interesting and promising antibacterial activity in the pharmaceutical, food and cosmetic industries.

scholarly journals Synergistic anticryptosporidial potential of the combination alpha-1-antitrypsin and paromomycin.

1997 ◽  
Vol 41 (9) ◽  
pp. 2006-2008 ◽  
Author(s):  
J R Forney ◽  
S Yang ◽  
M C Healey
Keyword(s):  
Inhibitory Concentration ◽  
Combined Treatment ◽  
Serine Protease Inhibitor ◽  
Synergistic Activity ◽  
Combined Treatments ◽  
Treatment Groups ◽  
The Mean ◽  
Alpha 1 Antitrypsin ◽  
Concentration Indices

The combined effect of the serine protease inhibitor alpha-1-antitrypsin (AAT) and the aminoglycoside paromomycin on Cryptosporidium parvum infection in vitro was investigated. AAT and paromomycin were mixed with C. parvum oocysts as either single or combined treatments and used to inoculate epithelial cell cultures. Single- and combined-treatment groups had significantly lower (P < 0.01) parasite numbers than untreated controls. The mean fractional inhibitory concentration indices suggested significant synergistic activity.

scholarly journals Evaluation and Comparison of Antibacterial Efficacy of Herbal Extracts in Combination with Antibiotics on Periodontal pathobionts: An in vitro Microbiological Study

Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 89 ◽  
Author(s):  
Shahabe Abullais Saquib ◽  
Nabeeh Abdullah AlQahtani ◽  
Irfan Ahmad ◽  
Mohammed Abdul Kader ◽  
Sami Saeed Al Shahrani ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Plant Extracts ◽  
Pathogenic Bacteria ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Synergistic Activity ◽  
Antibacterial Efficacy ◽  
Herbal Extracts ◽  
Inhibition Zones

Background: In the past few decades focus of research has been toward herbal medicines because of growing bacterial resistance and side effects of antimicrobial agents. The extract derived from the plants may increase the efficacy of antibiotics when used in combination against pathogenic bacteria. In the current study, the synergistic antibacterial efficacy of plant extracts in combination with antibiotics has been assessed on selected periodontal pathogens. Methods: Ethanolic extracts were prepared from Salvadora persica (Miswak) and Cinnamomum zeylanicum (Ceylon cinnamon), by the soxhalate method. Plaque samples were collected from clinical periodontitis patients to isolate and grow the periodontal pathobionts under favorable conditions. Susceptibility of bacteria to the extracts was assessed by gauging the diameter of the inhibition zones. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of plant extracts were determined against each bacterium. Synergistic activity of plants extract in combination with antibiotics against the bacteria was also assessed by measuring the diameter of the inhibition zones. Results: Ethanolic extract of both the plants showed an inhibitory effect on the proliferation and growth of all four strains of periodontal pathobionts. Maximum antibacterial activity was exhibited by C. zeylanicum against Tannerella forsythia (MIC = 1.56 ± 0.24 mg/mL, MBC = 6.25 ± 0.68 mg/mL), whereas among all the studied groups the minimum activity was reported by C. zeylanicum against Aggregatibacter actinomycetemcomitans the (MIC = 12.5 ± 3.25 mg/mL, MBC = 75 ± 8.23 mg/mL). Combination of herbal extracts with different antibiotics revealed a synergistic antibacterial effect. The best synergism was exhibited by S. persica with metronidazole against A. actinomycetemcomitans (27 ± 1.78). Conclusions: Current in vitro study showed variable antibacterial activity by experimented herbal extracts against periodontal pathobionts. The synergistic test showed significant antibacterial activity when plant extracts were combined with antibiotics.

Pharmacological interactions of TKIs with the P-gp drug transport protein.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2536-2536 ◽  
Author(s):  
Sandra Roche ◽  
Kasper Pedersen ◽  
Grainne Dunne ◽  
Denis Collins ◽  
Aoife Devery ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Drug Transport ◽  
Kinase Inhibitors ◽  
Resistance Mechanisms ◽  
Cancer Drug ◽  
Clear Understanding ◽  
Pharmacological Interactions

2536 Background: Tyrosine Kinase Inhibitors (TKIs) can interact with drug transport proteins. P-gp is a transporter with two important roles in cancer drug therapy. If overexpressed in tumour cells it can cause drug resistance. However, P-gp, expressed in tissues as part of normal drug clearance mechanisms, is also involved in termination of drug action. Hence, TKI-mediated interactions with P-gp have significant therapeutic consequences. Methods: P-gp over-expressing cancer cell lines were used to determine the inhibitor or substrate status of tyrosine kinase inhibitors (erlotinib, gefitinib, lapatinib, dasatinb, neratinib, afatinib and pazopanib). Cell proliferation assays in combination with a potent P-gp inhibitor, or P-gp substrate were also employed. Findings were augmented using LC-MS-based quantitation of cellular levels of target drugs. Results: We summarise our findings of four distinct interactions with P-gp among various TKIs. Some agents have little interaction at conventional doses; others can act as P-gp inhibitors without being substrates; substrates without being inhibitors or substrates which also prevent the actions of the transporter.Eachof the investigated TKIs has a distinct relationship with P-gp. As examples, lapatinib is an inhibitor but not a substrate, dasatinib is a substrate but not an inhibitor, while pazopanib has little interaction with P-gp. Other agents also have an effect on or are affected by P-gp to varying amounts with some of these interactions likely to be suprapharmacological. Conclusions: P-gp protein has important roles both in resistance and drug toxicology, hence, a clear understanding of the interaction of emerging drugs with this transporter is vital. Agents which are inhibitors of P-gp may have applications in drug resistance circumvention but may also greatly exacerbate the toxicity of concurrently administered P-gp substrate cytotoxics; conversely the activity of P-gp substrate TKIs may be reduced by tumour overexpression of the transporter. Hence in vitro screening of TKI-transporter interactions may identify putative TKI resistance mechanisms, help guide the development of combination schedule trials and/or reducing unwanted treatment side effects.

scholarly journals Transmission of infectious drug resistance from animals to man

1973 ◽  
Vol 71 (1) ◽  
pp. 209-215 ◽  
Author(s):  
D. M. Wells ◽  
O. B. James
Keyword(s):  
Drug Resistance ◽  
Antibiotic Resistance ◽  
Antibiotic Treatment ◽  
Farm Animals ◽  
Antibiotic Resistant ◽  
R Factor ◽  
Resistance Patterns ◽  
Antibiotic Resistance Patterns ◽  
R Factors

SUMMARYThe antibiotic resistance patterns of coliforms in faecal specimens from pigs and their human contacts were studied. The ability of the resistant coliforms to transfer their resistance in vitro to antibiotic-sensitive recipients was examined. The results showed that pigs which had received antibiotics carried more multiply-resistant, R-factor bearing coliforms than pigs which had not been given antibiotics. Human contacts of the antibiotic-treated pigs had a higher incidence of antibiotic-resistant coliforms with R-factors than human contacts of pigs which had not been given antibiotics. It is concluded that antibiotic treatment of farm, animals may lead to acquisition of antibiotic resistance by gut coliforms of man.

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