Colicin-like bacteriocins as novel therapeutic agents for the treatment of chronic biofilm-mediated infection

2012 ◽  
Vol 40 (6) ◽  
pp. 1549-1552 ◽  
Author(s):  
Carla L. Brown ◽  
Karen Smith ◽  
Laura McCaughey ◽  
Daniel Walker
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Antimicrobial Treatment ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Wide Range ◽  
Species Specific

The emergence of pan-resistant strains of Gram-negative pathogens and the ability of many bacteria to form multidrug-resistant biofilms during chronic infection poses the grave threat of bacterial infections that are truly untreatable with our current armoury of antibiotics. Despite obvious clinical need, few new antibiotics have entered clinical practice in recent years. For ‘difficult to treat’ Gram-negative bacteria such as Pseudomonas aeruginosa and Escherichia coli, where the presence of outer membrane and multidrug-efflux pumps severely limit the effectiveness of whole classes of antibiotics, the need is particularly pressing. An alternative approach to antimicrobial treatment is to use the well-characterized species-specific colicin-like bacteriocins which are produced by a wide range of Gram-negative bacteria, including Pseudomonas aeruginosa and Escherichia coli. Our current work on colicin-like bacteriocins aims to determine whether these potent antimicrobial agents are effective at killing bacteria growing in the biofilm state and during infection.

scholarly journals Gram Negative Bacteria (GNB) Isolated From Used Home-made and Surgical Nose/Face Mask by Local Residents of Akungba Akoko, Ondo State, a Threat to Life and False Sense of Protection against SARS-CoV-2 (COVID-19)

2021 ◽  
pp. 1-17
Author(s):  
Oludare Temitope Osuntokun
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Proteus Mirabilis ◽  
Antimicrobial Agents ◽  
Face Mask ◽  
Gram Negative Bacteria ◽  
Haemophilus Influenza ◽  
Gram Negative ◽  
False Sense ◽  
Zones Of Inhibition

Nose/Face masks are physical barriers to respiratory droplets that may enter through the nose and mouth to cause infections in the respiratory tract. The study was determined and assess the presence of Gram-negative bacteria in used home-made and surgical nose mask by residents of Akungba-Akoko Ondo State and to determine the antimicrobial susceptibility and resistant profile of the isolated bacteria to eight (8) different antimicrobial agents. The antimicrobial analysis were performed using standard microbiological and biochemical methods. Antimicrobial Susceptibility test of all identified isolates to antimicrobial agents were determined using the standard Kirby-Bauer disk diffusion method. The Gram-negative bacteria that were detected from the used home-made and surgical nose mask in this study include: Haemophilus influenza, Proteus mirabilis, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumonia. During this study, all the Gram-negative bacteria isolates were resistant to Ciproflox in both used home-made and surgical nose mask. All isolates were also resistant to Ampicilin, Augmentin, Septrin and Streptomycin. In this study, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa were isolated organism from used home-made nose mask, it was observed that Escherichia coli were resistant to Augmentin, Tarivid, Ciproflox, Gentamycin, and Reflaxine, and Pseudomonas aeruginosa were resistant to Tarivid, Ciproflox, and Nalidixic acid between 20 mm and 24 mm zones of inhibition respectively. Haemophilus influenza, Pseudomonas aeruginosa, Escherichia coli and Proteus mirabilis were isolated organism from used surgical nose mask. It was observed that all isolated organisms from the used surgical nose/face mask were resistant to Augmentin and Gentamycin between 20 and 24 mm zones of inhibition respectively. Klebsiella pneumoniae were isolated from both used home-made and surgical nose/face mask and were found to be resistant to Streptomycin, Septrin, Ampicilin, and Gentamicin between 20 to 22 mm zones of inhibition respectively. Proteus mirabilis were isolated from used surgical nose/face mask,        they were found to be resistant to Ciproflox at 21mm zones of inhibition. Haemophilus influenza were resistant to Ampicilin, Septrin, Streptomycin, and Augmentin at 23 mm zones of inhibition. Isolates from used both home-made and surgical nose/face mask were subjected to modified and synergized antibiotics, it was observed that the isolates from both used home-made and surgical nose mask were resistant to all modified and synergized antibiotics between 20 and 25 mm zones of inhibition respectively. The result of this study validates the potency of  Gram negative bacteria isolated from used both home-made and surgical nose/face mask and the degree of invasion and evasiveness, thereby causing various degrees of infections and a false sense of protection against SARS-CoV-2 (COVID-19). Finding from this research recommends a stringent measures were needed to be implemented, to halt and combat this revenging situation especially in the new era of mutating SARS-CoV-2 Virus not only in Nigeria, worldwide at large.

scholarly journals Bacteriocins, Antimicrobial Peptides from Bacterial Origin: Overview of Their Biology and Their Impact against Multidrug-Resistant Bacteria

2020 ◽  
Vol 8 (5) ◽  
pp. 639 ◽  
Author(s):  
Alexis Simons ◽  
Kamel Alhanout ◽  
Raphaël E. Duval
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Further Development

Currently, the emergence and ongoing dissemination of antimicrobial resistance among bacteria are critical health and economic issue, leading to increased rates of morbidity and mortality related to bacterial infections. Research and development for new antimicrobial agents is currently needed to overcome this problem. Among the different approaches studied, bacteriocins seem to be a promising possibility. These molecules are peptides naturally synthesized by ribosomes, produced by both Gram-positive bacteria (GPB) and Gram-negative bacteria (GNB), which will allow these bacteriocin producers to survive in highly competitive polymicrobial environment. Bacteriocins exhibit antimicrobial activity with variable spectrum depending on the peptide, which may target several bacteria. Already used in some areas such as agro-food, bacteriocins may be considered as interesting candidates for further development as antimicrobial agents used in health contexts, particularly considering the issue of antimicrobial resistance. The aim of this review is to present an updated global report on the biology of bacteriocins produced by GPB and GNB, as well as their antibacterial activity against relevant bacterial pathogens, and especially against multidrug-resistant bacteria.

scholarly journals Correlated Transcriptional Responses Provide Insights into the Synergy Mechanisms of the Furazolidone, Vancomycin, and Sodium Deoxycholate Triple Combination in Escherichia coli

mSphere ◽  
2021 ◽  
Author(s):  
Catrina Olivera ◽  
Murray P. Cox ◽  
Gareth J. Rowlands ◽  
Jasna Rakonjac
Keyword(s):  
Escherichia Coli ◽  
Bacterial Infections ◽  
Sodium Deoxycholate ◽  
Multidrug Resistant ◽  
Alternative Strategy ◽  
Gram Negative Bacteria ◽  
Triple Combination ◽  
Transcriptional Responses ◽  
Promising Alternative ◽  
Gram Negative

Synergistic antibiotic combinations are a promising alternative strategy for developing effective therapies for multidrug-resistant bacterial infections. The synergistic combination of the existing antibiotics nitrofurans and vancomycin with sodium deoxycholate shows promise in inhibiting and killing multidrug-resistant Gram-negative bacteria.

MULTI-RESISTANT CARBAPENEM-INSENSITIVE GRAMNEGATIVE BACTERIA IN PATIENTS WITH SOLID TUMORS

2017 ◽  
Vol 63 (5) ◽  
pp. 780-784
Author(s):  
Anna Polishchuk ◽  
Yelena Yakubovich ◽  
Viktor Osovskikh ◽  
Vladimir Yevtushenko ◽  
O. Polukhina
Keyword(s):  
Cancer Patients ◽  
Solid Tumors ◽  
Antimicrobial Agents ◽  
Distinct Species ◽  
Multidrug Resistant ◽  
Klebsiella Pneumonia ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Wide Range ◽  
Genes Encoding

Infections caused by multiresistant gram-negative bacteria are one of the major problems in the treatment of cancer patients. Strains with mechanisms of resistance mediated by carbapenemases represent a particular threat since they spread rapidly and are characterized by high frequency of occurrence of multiresistance to antimicrobial agents. Here we show that 14 out of 399 gram-negative bacteria (3,5 %), isolated from clinical specimens of 11 patients with solid tumors (n=581) in a hospital of federal level in January 2015-April 2016 were carbapenem-insusceptible. Among them 3 isolates of Klebsiella pneumonia, 2 Enterobacter cloacae, 2 Pseudomonas aeruginosa and 7 Acinetobacter baumannii. All 14 strains were resistant to a wide range of antimicrobial agents including beta-lactams, aminoglycosides, monobactams and fluoroquinolones. The only antimicrobial agent to which all but one Exloacae strain remained susceptible was colistin. This strain was insusceptible to all 10 antimicrobial agents tested in the study, including tigecycline. We observed two cases of infection of a single patient by 2-3 distinct species of multidrug-resistant gram-negative bacteria. In 79 % of the strains the genes encoding carbapenemases of OXA40/24, KPC, VIM and NDM types were detected. Despite the fact that multidrug-resistant car-bapenem-insusceptible strains of gram-negative bacteria were isolated from a relatively small number of cancer patients, the majority of these strains represent a particular epidemiological and clinical threat.

scholarly journals New β-Lactamase Inhibitors: a Therapeutic Renaissance in an MDR World

2013 ◽  
Vol 58 (4) ◽  
pp. 1835-1846 ◽  
Author(s):  
Sarah M. Drawz ◽  
Krisztina M. Papp-Wallace ◽  
Robert A. Bonomo
Keyword(s):  
Bacterial Infections ◽  
Clinical Problem ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Therapeutic Approaches ◽  
Preclinical Development ◽  
Gram Negative ◽  
The Past ◽  
Wide Range ◽  
Dosing Regimens

ABSTRACTAs the incidence of Gram-negative bacterial infections for which few effective treatments remain increases, so does the contribution of drug-hydrolyzing β-lactamase enzymes to this serious clinical problem. This review highlights recent advances in β-lactamase inhibitors and focuses on agents with novel mechanisms of action against a wide range of enzymes. To this end, we review the β-lactamase inhibitors currently in clinical trials, select agents still in preclinical development, and older therapeutic approaches that are being revisited. Particular emphasis is placed on the activity of compounds at the forefront of the developmental pipeline, including the diazabicyclooctane inhibitors (avibactam and MK-7655) and the boronate RPX7009. With its novel reversible mechanism, avibactam stands to be the first new β-lactamase inhibitor brought into clinical use in the past 2 decades. Our discussion includes the importance of selecting the appropriate partner β-lactam and dosing regimens for these promising agents. This “renaissance” of β-lactamase inhibitors offers new hope in a world plagued by multidrug-resistant (MDR) Gram-negative bacteria.

scholarly journals Magnitude of Multidrug Resistance among Bacterial Isolates from Surgical Site Infections in Two National Referral Hospitals in Asmara, Eritrea

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Eyob Yohannes Garoy ◽  
Yacob Berhane Gebreab ◽  
Oliver Okoth Achila ◽  
Nobiel Tecklebrhan ◽  
Hermon Michael Tsegai ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Agents ◽  
Surgical Site Infections ◽  
Diffusion Method ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Referral Hospitals

Background. The World Health Organization has emphasized the importance of understanding the epidemiology of MDR organisms from a local standpoint. Here, we report on a spectrum of bacteria associated with surgical site infections in two referral hospitals in Eritrea and the associated antibiotic susceptibility patterns. Methods. This survey was conducted between February and May 2017. A total of 83 patients receiving treatment for various surgical conditions were included. Swabs from infected surgical sites were collected using Levine technique and processed using standard microbiological procedures. In vitro antimicrobial susceptibility testing was performed on Mueller–Hinton Agar by the Kirby-Bauer disk diffusion method following Clinical and Laboratory Standards Institute guidelines. The data were analyzed using SPSS version 20. Results. A total of 116 isolates were recovered from 83 patients. In total, 67 (58%) and 49 (42%) of the isolates were Gram-positive and Gram-negative bacteria, respectively. The most common isolates included Citrobacter spp., Klebsiella spp., Escherichia coli, Proteus spp., Pseudomonas aeruginosa, Salmonella spp., Enterobacter spp., and Acinetobacter spp. In contrast, Staphylococcus aureus, CONS, and Streptococcus viridians were the predominant Gram-positive isolates. All the Staphylococcus aureus isolates were resistant to penicillin. MRSA phenotype was observed in 70% of the isolates. Vancomycin, clindamycin, and erythromycin resistance were observed in 60%, 25%, and 25% of the isolates, respectively. Furthermore, a high proportion (91%) of the Gram-negative bacteria were resistant to ampicillin and 100% of the Pseudomonas aeruginosa and Escherichia coli isolates were resistant to >5 of the tested antibiotics. The two Acinetobacter isolates were resistant to >7 antimicrobial agents. We also noted that 4 (60%) of the Klebsiella isolates were resistant to >5 antimicrobial agents. Possible pan-drug-resistant (PDR) strains were also isolated. Conclusion. Due to the high frequency of MDR isolates reported in this study, the development and implementation of suitable infection control policies and guidelines is imperative.

scholarly journals Novel Ethyl 1,5-Disubstituted-1H-Pyrazole-3-Carboxylates as a New Class of Antimicrobial Agents

2014 ◽  
Vol 64 (3) ◽  
pp. 335-344 ◽  
Author(s):  
Awwad A. Radwan ◽  
Mostafa M. Ghorab ◽  
Mansour S. Alsaid ◽  
Fares K. Alanazi
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Candida Albicans ◽  
Antimicrobial Agents ◽  
Gram Negative Bacteria ◽  
Pyrazole Derivatives ◽  
Reference Drug ◽  
Gram Negative ◽  
New Class

Abstract A series of pyrazole derivatives 9-22 were designed and synthesized. All the newly synthesized compounds were assayed for their antimicrobial activity against the Grampositive bacteria Staphyllococcus aureus and Bacillius subtilis and the Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa, in addition to the fungi organisms, Candida albicans, C. parapsilosis and C. tropicalis. Ethyl 5-(2,5-dimethylthiophen- 3-yl)-1-phenyl-1H-pyrazole-3-carboxylate (21) (MICE.coli = 0.038 μmol mL-1, MICP. aerug. = 0.067 μmol mL-1) is nearly as active as ampicillin (MIC = 0.033 and 0.067 μmol mL-1), respectively. Ethyl 5-(4-bromo-2-chlorophenyl)- 1-phenyl-1H-pyrazole-3-carboxylate (16) (MIC = 0.015 μmol mL-1) is more active than fluconazole (0.020 μmol mL-1) as a reference drug against C. parapsilosis.

scholarly journals In-Vitro Efficacy of Cefiderocol in Carbapenem-Non-Susceptible Gram-Negative Bacilli of Different Genotypes in Sub-Region of North Rhine Westphalia, Germany

Pathogens ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1258
Author(s):  
Beniam Ghebremedhin ◽  
Parviz Ahmad-Nejad
Keyword(s):  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Acinetobacter Baumanii ◽  
In Vitro Susceptibility ◽  
Gram Negative ◽  
Therapy Options ◽  
Wide Range ◽  
Testing Susceptibility ◽  
Species Specific

In the last two decades, the worldwide dissemination of multidrug-resistant Gram-negative bacteria (MDR-GNB) has continued. Therapy options for such infections caused by MDR-GNB remain scarce, and only few new antimicrobial agents have been granted market approval. Cefiderocol has been approved for the treatment of infections associated with aerobic GNB with limited therapy options. This study evaluated the in vitro efficacy of cefiderocol against carbapenem-non-susceptible clinical GNB isolates from Germany. A total of 115 non-duplicate carbapenem-nonsusceptible GNB isolates, 61 (53.05%) of which were Enterobacterales species and 54 (46.95%) were non-fermenters (Acinetobacter baumanii and Pseudomonas aeruginosa), were investigated for their cefiderocol susceptibility. Minimum inhibitory concentrations (MICs) for cefiderocol were determined by disk diffusion, according to EUCAST (European committee for antimicrobial susceptibility testing). Susceptibility rates were based on EUCAST breakpoints. In the absence of a species-specific breakpoint, pharmacokinetic/-dynamic breakpoints were used. The most common pathogen was A. baumannii (33.91%), followed by Klebsiella pneumoniae (31.3%), P. aeruginosa (13.04%) and Escherichia coli (9.57%). Overall, 83.6% (51/61) of the Enterobacterales and 81.48% (44/54) of the non-fermenters were susceptible towards cefiderocol. In total, 20 species of Enterobacterales and non-fermenting GNB were resistant towards cefiderocol, irrespective of the isolation year (2014 to 2021). Moreover, the majority of the resistant isolates were among the OXA-23 producing A. baumannii (n = 7/26; 26.92%) from patients hospitalized during 2018 and 2019. Cefiderocol demonstrated high in vitro susceptibility rates against a wide range of carbapenem-non-susceptible GNB, including carbapenemase-producing isolates. Cefiderocol exhibited stability against hydrolysis by all carbapenemases, including metallo-β-lactamases (MBLs), except that few OXA-producing isolates exhibited resistance towards cefiderocol.

Synthesis, In Vitro and In Silico Studies of Indolequinone Derivatives against Clinically Relevant Bacterial Pathogens

2020 ◽  
Vol 20 (3) ◽  
pp. 192-208 ◽  
Author(s):  
Talita Odriane Custodio Leite ◽  
Juliana Silva Novais ◽  
Beatriz Lima Cosenza de Carvalho ◽  
Vitor Francisco Ferreira ◽  
Leonardo Alves Miceli ◽  
...  
Keyword(s):  
In Silico ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Mass Spectrometry Analysis ◽  
World Health ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Dione Derivative ◽  
In Silico Studies

Background: According to the World Health Organization, antimicrobial resistance is one of the most important public health threats of the 21st century. Therefore, there is an urgent need for the development of antimicrobial agents with new mechanism of action, especially those capable of evading known resistance mechanisms. Objective: We described the synthesis, in vitro antimicrobial evaluation, and in silico analysis of a series of 1H-indole-4,7-dione derivatives. Methods: The new series of 1H-indole-4,7-diones was prepared with good yield by using a copper(II)- mediated reaction between bromoquinone and β-enamino ketones bearing alkyl or phenyl groups attached to the nitrogen atom. The antimicrobial potential of indole derivatives was assessed. Molecular docking studies were also performed using AutoDock 4.2 for Windows. Characterization of all compounds was confirmed by one- and two-dimensional NMR techniques 1H and 13C NMR spectra [1H, 13C – APT, 1H x 1H – COSY, HSQC and HMBC], IR and mass spectrometry analysis. Results: Several indolequinone compounds showed effective antimicrobial profile against Grampositive (MIC = 16 µg.mL-1) and Gram-negative bacteria (MIC = 8 µg.mL-1) similar to antimicrobials current on the market. The 3-acetyl-1-(2,5-dimethylphenyl)-1H-indole-4,7-dione derivative exhibited an important effect against different biofilm stages formed by a serious hospital life-threatening resistant strain of Methicillin-Resistant Staphylococcus aureus (MRSA). A hemocompatibility profile analysis based on in vitro hemolysis assays revealed the low toxicity effects of this new series. Indeed, in silico studies showed a good pharmacokinetics and toxicological profiles for all indolequinone derivatives, reinforcing their feasibility to display a promising oral bioavailability. An elucidation of the promising indolequinone derivatives binding mode was achieved, showing interactions with important sites to biological activity of S. aureus DNA gyrase. These results highlighted 3-acetyl-1-(2-hydroxyethyl)-1Hindole- 4,7-dione derivative as broad-spectrum antimicrobial prototype to be further explored for treating bacterial infections. Conclusion: The highly substituted indolequinones were obtained in moderate to good yields. The pharmacological study indicated that these compounds should be exploited in the search for a leading substance in a project aimed at obtaining new antimicrobials effective against Gram-negative bacteria.

scholarly journals MexAB-OprM Efflux Pump Interaction with the Peptidoglycan of Escherichia coli and Pseudomonas aeruginosa

2021 ◽  
Vol 22 (10) ◽  
pp. 5328
Author(s):  
Miao Ma ◽  
Margaux Lustig ◽  
Michèle Salem ◽  
Dominique Mengin-Lecreulx ◽  
Gilles Phan ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Cell Division ◽  
Membrane Proteins ◽  
Outer Membrane ◽  
Efflux Pump ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Active Efflux

One of the major families of membrane proteins found in prokaryote genome corresponds to the transporters. Among them, the resistance-nodulation-cell division (RND) transporters are highly studied, as being responsible for one of the most problematic mechanisms used by bacteria to resist to antibiotics, i.e., the active efflux of drugs. In Gram-negative bacteria, these proteins are inserted in the inner membrane and form a tripartite assembly with an outer membrane factor and a periplasmic linker in order to cross the two membranes to expulse molecules outside of the cell. A lot of information has been collected to understand the functional mechanism of these pumps, especially with AcrAB-TolC from Escherichia coli, but one missing piece from all the suggested models is the role of peptidoglycan in the assembly. Here, by pull-down experiments with purified peptidoglycans, we precise the MexAB-OprM interaction with the peptidoglycan from Escherichia coli and Pseudomonas aeruginosa, highlighting a role of the peptidoglycan in stabilizing the MexA-OprM complex and also differences between the two Gram-negative bacteria peptidoglycans.

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