scholarly journals Bacterial behavior in human blood reveals complement evaders with persister-like features

2020 ◽  
Author(s):  
Stéphane Pont ◽  
Nathan Fraikin ◽  
Yvan Caspar ◽  
Laurence Van Melderen ◽  
Ina Attrée ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Human Blood ◽  
Immune Cells ◽  
Bacterial Load ◽  
Phenotypic Heterogeneity ◽  
Health Concern ◽  
Resistant Bacteria ◽  
Bacterial Cells ◽  
Human Pathogens ◽  
Bacterial Strains

AbstractsBacterial bloodstream infections (BSI) are a major health concern and can cause up to 40% mortality. Pseudomonas aeruginosa BSI is often of nosocomial origin and is associated with a particularly poor prognosis. The mechanism of bacterial persistence in blood is still largely unknown. Here, we analyzed the behavior of a cohort of clinical and laboratory Pseudomonas aeruginosa strains in human blood. In this specific environment, complement was the main defensive mechanism, acting either by direct bacterial lysis or by opsonophagocytosis, which required recognition by immune cells. We found highly variable survival rates for different strains in blood, whatever their origin, serotype, or the nature of their secreted toxins and despite their detection by immune cells. We identified and characterized a complement-tolerant subpopulation of bacterial cells that we named “evaders”. Evaders represented 0.1-0.001% of the initial bacterial load and displayed transient tolerance. Although evaders shared some features with bacterial persisters, which tolerate antibiotic treatment, they appear to have evolved distinct strategies to escape complement. We detected the evaders for five other major human pathogens: Acinetobacter baumannii, Burkholderia multivorans, enteroaggregative Escherichia coli, Klebsiella pneumoniae, and Yersinia enterocolitica. Thus, the evaders could allow the pathogen to persist within the bloodstream, and may be the cause of fatal bacteremia or dissemination, notably in the absence of effective antibiotic treatments.Author summary for “Complement evaders”Blood infections by antibiotic resistant bacteria, notably Pseudomonas aeruginosa, are major concerns in hospital settings. The complex interplay between P. aeruginosa and the innate immune system in the context of human blood is still poorly understood. By studying the behavior of various P. aeruginosa strains in human whole blood and plasma, we showed that bacterial strains display different rate of tolerance to the complement system. Despite the complement microbicide activity, most bacteria withstand elimination through phenotypic heterogeneity creating a tiny (<0.1%) subpopulation of transiently tolerant evaders. While genetically identical to the rest of the complement-sensitive population, evaders allow the bacteria to persist in plasma. This phenotypic heterogeneity thus prevents total elimination of the pathogen from the circulation, and represent a new strategy to disseminate within the organism.

scholarly journals Bacterial behavior in human blood reveals complement evaders with some persister-like features

2020 ◽  
Vol 16 (12) ◽  
pp. e1008893
Author(s):  
Stéphane Pont ◽  
Nathan Fraikin ◽  
Yvan Caspar ◽  
Laurence Van Melderen ◽  
Ina Attrée ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Human Blood ◽  
Immune Cells ◽  
Bacterial Load ◽  
Survival Rates ◽  
Bloodstream Infections ◽  
Health Concern ◽  
Bacterial Cells ◽  
Human Pathogens ◽  
Different Strains

Bacterial bloodstream infections (BSI) are a major health concern and can cause up to 40% mortality. Pseudomonas aeruginosa BSI is often of nosocomial origin and is associated with a particularly poor prognosis. The mechanism of bacterial persistence in blood is still largely unknown. Here, we analyzed the behavior of a cohort of clinical and laboratory Pseudomonas aeruginosa strains in human blood. In this specific environment, complement was the main defensive mechanism, acting either by direct bacterial lysis or by opsonophagocytosis, which required recognition by immune cells. We found highly variable survival rates for different strains in blood, whatever their origin, serotype, or the nature of their secreted toxins (ExoS, ExoU or ExlA) and despite their detection by immune cells. We identified and characterized a complement-tolerant subpopulation of bacterial cells that we named “evaders”. Evaders shared some features with bacterial persisters, which tolerate antibiotic treatment. Notably, in bi-phasic killing curves, the evaders represented 0.1–0.001% of the initial bacterial load and displayed transient tolerance. However, the evaders are not dormant and require active metabolism to persist in blood. We detected the evaders for five other major human pathogens: Acinetobacter baumannii, Burkholderia multivorans, enteroaggregative Escherichia coli, Klebsiella pneumoniae, and Yersinia enterocolitica. Thus, the evaders could allow the pathogen to persist within the bloodstream, and may be the cause of fatal bacteremia or dissemination, in particular in the absence of effective antibiotic treatments.

scholarly journals Analogues of a Cyclic Antimicrobial Peptide with a Flexible Linker Show Promising Activity against Pseudomonas aeruginosa and Staphylococcus aureus

Antibiotics ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 366 ◽  
Author(s):  
Thomas Thomsen ◽  
Helen Mendel ◽  
Wafaa Al-Mansour ◽  
Alberto Oddo ◽  
Anders Løbner-Olesen ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Health Concern ◽  
Side Chain ◽  
Resistant Bacteria ◽  
Bacterial Strains ◽  
Major Health ◽  
E Coli ◽  
Drug Resistant Bacteria ◽  
Multicellular Organisms

The emergence of multi-drug resistant bacteria is becoming a major health concern. New strategies to combat especially Gram-negative pathogens are urgently needed. Antimicrobial peptides (AMPs) found in all multicellular organisms act as a first line of defense in immunity. In recent years, AMPs have attracted increasing attention as potential antibiotics. Naturally occurring antimicrobial cyclic lipopeptides include colistin and daptomycin, both of which contain a flexible linker. We previously reported a cyclic AMP BSI-9 cyclo(Lys-Nal-Lys-Lys-Bip-O2Oc-Nal-Lys-Asn) containing a flexible linker, with a broad spectrum of activity against bacterial strains and low hemolytic activity. In this study, improvement of the antimicrobial activity of BSI-9, against the European Committee on Antimicrobial Susceptibility Testing (EUCAST) strains of S. aureus, E. coli, A. baumannii, and P. aeruginosa was examined. This led to synthesis of eighteen peptide analogues of BSI-9, produced in four individual stages, with a different focus in each stage; cyclization point, hydrophobicity, cationic side-chain length, and combinations of the last two. Specifically the modified compound 11, exhibited improved activity against Staphylococcus aureus and Pseudomonas aeruginosa with MIC of 4 µg/mL and 8 µg/mL, respectively, compared to the original BSI-9, which had an MIC of 16–32 µg/mL.

scholarly journals Advances in Antarctic Research for Antimicrobial Discovery: A Comprehensive Narrative Review of Bacteria from Antarctic Environments as Potential Sources of Novel Antibiotic Compounds Against Human Pathogens and Microorganisms of Industrial Importance

Antibiotics ◽  
2018 ◽  
Vol 7 (4) ◽  
pp. 90 ◽  
Author(s):  
Kattia Núñez-Montero ◽  
Leticia Barrientos
Keyword(s):  
Public Health Problem ◽  
Narrative Review ◽  
Bioactive Molecules ◽  
Resistant Bacteria ◽  
Natural Environments ◽  
Antimicrobial Compounds ◽  
Human Pathogens ◽  
Bacterial Strains ◽  
Antarctic Bacteria ◽  
Recent Emergence

The recent emergence of antibiotic-resistant bacteria has become a critical public health problem. It is also a concern for industries, since multidrug-resistant microorganisms affect the production of many agricultural and food products of economic importance. Therefore, discovering new antibiotics is crucial for controlling pathogens in both clinical and industrial spheres. Most antibiotics have resulted from bioprospecting in natural environments. Today, however, the chances of making novel discoveries of bioactive molecules from various well-known sources have dramatically diminished. Consequently, unexplored and unique environments have become more likely avenues for discovering novel antimicrobial metabolites from bacteria. Due to their extreme polar environment, Antarctic bacteria in particular have been reported as a potential source for new antimicrobial compounds. We conducted a narrative review of the literature about findings relating to the production of antimicrobial compounds by Antarctic bacteria, showing how bacterial adaptation to extreme Antarctic conditions confers the ability to produce these compounds. We highlighted the diversity of antibiotic-producing Antarctic microorganisms, including the phyla Proteobacteria, Actinobacteria, Cyanobacteria, Firmicutes, and Bacteroidetes, which has led to the identification of new antibiotic molecules and supports the belief that research on Antarctic bacterial strains has important potential for biotechnology applications, while providing a better understanding of polar ecosystems.

scholarly journals Occurrence of Bacterial Markers and Antibiotic Resistance Genes in Sub-Saharan Rivers Receiving Animal Farm Wastewaters

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Dhafer Mohammed M. Al Salah ◽  
Amandine Laffite ◽  
John Poté
Keyword(s):  
Developing Countries ◽  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Bacterial Load ◽  
Antibiotic Resistance Genes ◽  
Health Concern ◽  
Resistant Bacteria ◽  
P Value ◽  
Animal Farm ◽  
Sources Of Contamination

Abstract Antibiotic resistant bacteria and genes which confer resistance to antibiotics from human/animal sources are currently considered a serious environmental and a public health concern. This problem is still little investigated in aquatic environment of developing countries according to the different climatic conditions. In this research, the total bacterial load, the abundance of relevant bacteria (Escherichia coli (E. coli), Enterococcus (Ent), and Pseudomonas), and antibiotic resistance genes (ARGs: blaOXA-48, blaCTX-M, sul1, sul2, sul3, and tet(B)) were quantified using Quantitative Polymerase Chain Reaction (qPCR) in sediments from two rivers receiving animal farming wastewaters under tropical conditions in Kinshasa, capital city of the Democratic Republic of the Congo. Human and pig host-specific markers were exploited to examine the sources of contamination. The total bacterial load correlated with relevant bacteria and genes blaOXA-48, sul3, and tet(B) (P value < 0.01). E. coli strongly correlated with 16s rDNA, Enterococcus, Pseudomonas spp., blaOXA-48, sul3, and tet(B) (P value < 0.01) and with blaCTX-M, sul1, and sul2 at a lower magnitude (P value < 0.05). The most abundant and most commonly detected ARGs were sul1, and sul2. Our findings confirmed at least two sources of contamination originating from pigs and anthropogenic activities and that animal farm wastewaters didn’t exclusively contribute to antibiotic resistance profile. Moreover, our analysis sheds the light on developing countries where less than adequate infrastructure or lack of it adds to the complexity of antibiotic resistance proliferation with potential risks to the human exposure and aquatic living organisms. This research presents useful tools for the evaluation of emerging microbial contaminants in aquatic ecosystems which can be applied in the similar environment.

Antibiotic Resistance and Phylogenetic Characterization of Acinetobacter baumannii Strains Isolated from Commercial Raw Meat in Switzerland

2014 ◽  
Vol 77 (11) ◽  
pp. 1976-1981 ◽  
Author(s):  
AGNESE LUPO ◽  
DEBORA VOGT ◽  
SALOME N. SEIFFERT ◽  
ANDREA ENDIMIANI ◽  
VINCENT PERRETEN
Keyword(s):  
Acinetobacter Baumannii ◽  
Antibiotic Susceptibility ◽  
Multidrug Resistant ◽  
Health Concern ◽  
Fourth Generation ◽  
Pcr Analysis ◽  
Resistant Bacteria ◽  
Human Pathogens ◽  
Raw Meat ◽  
Phylogenetic Characterization

The spread of antibiotic-resistant bacteria through food has become a major public health concern because some important human pathogens may be transferred via the food chain. Acinetobacter baumannii is one of the most life-threatening gram-negative pathogens; multidrug-resistant (MDR) clones of A. baumannii are spreading worldwide, causing outbreaks in hospitals. However, the role of raw meat as a reservoir of A. baumannii remains unexplored. In this study, we describe for the first time the antibiotic susceptibility and fingerprint (repetitive extragenic palindromic PCR [rep-PCR] profile and sequence types [STs]) of A. baumannii strains found in raw meat retailed in Switzerland. Our results indicate that A. baumannii was present in 62 (25.0%) of 248 (CI 95%: 19.7 to 30.9%) meat samples analyzed between November 2012 and May 2013, with those derived from poultry being the most contaminated (48.0% [CI 95%: 37.8 to 58.3%]). Thirty-nine strains were further tested for antibiotic susceptibility and clonality. Strains were frequently not susceptible (intermediate and/or resistant) to third- and fourth-generation cephalosporins for human use (i.e., ceftriaxone [65%], cefotaxime [32%], ceftazidime [5%], and cefepime [2.5%]). Resistance to piperacillin-tazobactam, ciprofloxacin, colistin, and tetracycline was sporadically observed (2.5, 2.5, 5, and 5%, respectively), whereas resistance to carbapenems was not found. The strains were genetically very diverse from each other and belonged to 29 different STs, forming 12 singletons and 6 clonal complexes (CCs), of which 3 were new (CC277, CC360, and CC347). Rep-PCR analysis further distinguished some strains of the same ST. Moreover, some A. baumannii strains from meat belonged to the clonal complexes CC32 and CC79, similar to the MDR isolates responsible for human infections. In conclusion, our findings suggest that raw meat represents a reservoir of MDR A. baumannii and may serve as a vector for the spread of these pathogens into both community and hospital settings.

scholarly journals Synthesis, Characterization, and Antimicrobial Activity of a Novel Trisazo Dye from 3-Amino-4H-thieno[3,4-c][1]benzopyran-4-one

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Joseph Tsemeugne ◽  
Emmanuel Sopbué Fondjo ◽  
Jean-de-Dieu Tamokou ◽  
Taoufik Rohand ◽  
Arnaud Djintchui Ngongang ◽  
...  
Keyword(s):  
Spectroscopic Data ◽  
2D Nmr ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Human Pathogens ◽  
Bacterial Strains ◽  
Antibacterial And Antifungal Activities ◽  
Diazonium Ion ◽  
Antibacterial And Antifungal ◽  
Susceptibility Assay

A new trisazo dye has been synthesized by coupling the diazonium ion of 3-amino-4H thieno[3,4-c][1]benzopyran-4-one with 2-tert-butyl-4-methoxyphenol. The newly prepared trisazo dye was characterized by its physical, elemental, and spectroscopic data. 2D-NMR (COSY, HSQC, and HMBC) techniques were used to secure the structural assignments. The new trisazo dye (compound 7) along with precursors 3, 4, and 6 was screened by microdilution susceptibility assay for antibacterial and antifungal activities towards eight bacterial strains and three yeasts selected on the basis of their relevance as human pathogens. The results showed that compound 7 (MIC = 2–128 μg/mL) was the most active as compared with its precursors. The most resistant microorganisms were V. cholerae NB2 and V. cholerae SG24, whereas the most sensitive microorganism was C. neoformans. The overall results of this study indicated that compound 7 had the greatest potential value against both yeasts and multidrug-resistant bacteria, so further investigation is warranted.

scholarly journals Activity of the Novel Peptide Arminin against Multiresistant Human Pathogens Shows the Considerable Potential of Phylogenetically Ancient Organisms as Drug Sources

2009 ◽  
Vol 53 (12) ◽  
pp. 5245-5250 ◽  
Author(s):  
René Augustin ◽  
Friederike Anton-Erxleben ◽  
Stephanie Jungnickel ◽  
Georg Hemmrich ◽  
Björn Spudy ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Multidrug Resistant ◽  
Proteolytic Processing ◽  
Erythrocyte Membranes ◽  
Resistant Bacteria ◽  
Minimal Bactericidal Concentration ◽  
Human Pathogens ◽  
Bacterial Strains ◽  
Multiresistant Bacteria ◽  
High Level

ABSTRACT The emergence of multidrug-resistant bacteria highlights the need for new antibacterial agents. Arminin 1a is a novel antimicrobial peptide discovered during investigations of the epithelial defense of the ancient metazoan Hydra. Following proteolytic processing, the 31-amino-acid-long positively charged C-terminal part of arminin 1a exhibits potent and broad-spectrum activity against bacteria, including multiresistant human pathogenic strains, such as methicillin-resistant Staphylococcus aureus (MRSA) strains (minimal bactericidal concentration, 0.4 μM to 0.8 μM). Ultrastructural observations indicate that bacteria are killed by disruption of the bacterial cell wall. Remarkably, the antibacterial activity of arminin 1a is not affected under the physiological salt conditions of human blood. In addition, arminin 1a is a selective antibacterial agent that does not affect human erythrocyte membranes. Arminin 1a shows no sequence homology to any known antimicrobial peptide. Because of its high level of activity against multiresistant bacterial strains pathogenic for humans, the peptide arminin 1a is a promising template for a new class of antibiotics. Our data suggest that ancient metazoan organisms such as Hydra hold promise for the detection of novel antimicrobial molecules and the treatment of infections caused by multiresistant bacteria.

scholarly journals Elastic Nanofibrous Membranes for Medical and Personal Protection Applications: Manufacturing, Anti-COVID-19, and Anti-Colistin Resistant Bacteria Evaluation

Polymers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 3987
Author(s):  
Latifah Abdullah Alshabanah ◽  
Nada Omran ◽  
Bassma H. Elwakil ◽  
Moaaz T. Hamed ◽  
Salwa M. Abdallah ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Metal Oxide ◽  
Reduction Rate ◽  
Resistant Bacteria ◽  
Bacterial Cells ◽  
Personal Protection ◽  
Bacterial Strains ◽  
Functional Layer ◽  
Oxide Concentration ◽  
Nanofiber Membranes

Herein, in the present work two series of thermoplastic polyurethane (TPU) nanofibers were manufactured using the electrospinning techniques with ZnO and CuO nanoparticles for a potential use as an elastic functional layer in antimicrobial applications. Percentages of 0%, 2 wt%, and 4 wt% of the nanoparticles were used. The morphological characterization of the electrospun TPU and TPU/NPs composites nanofibers were observed by using scanning electron microscopy to show the average fiber diameter and it was in the range of 90–150 nm with a significant impact of the nanoparticle type. Mechanical characterization showed that TPU nanofiber membranes exhibit excellent mechanical properties with ultra-high elastic properties. Elongation at break reached up to 92.5%. The assessment of the developed nanofiber membranes for medical and personal protection applications was done against various colistin resistant bacterial strains and the results showed an increment activity by increasing the metal oxide concentration up to 83% reduction rate by using TPU/ZnO 4% nanofibers against K. pneumoniae strain 10. The bacterial growth was completely eradicated after 8 and 16 h incubation with TPU/ZnO and TPU/CuO nanofibers, respectively. The nanofibers SEM study reveals the adsorption of the bacterial cells on the metal oxides nanofibers surface which led to cell lysis and releasing of their content. Finally, in vitro study against Spike S-protein from SARS-CoV-2 was also evaluated to investigate the potent effectiveness of the proposed nanofibers in the virus deactivation. The results showed that the metal oxide concentration is an effective factor in the antiviral activity due to the observed pattern of increasing the antibacterial and antiviral activity by increasing the metal oxide concentration; however, TPU/ZnO nanofibers showed a potent antiviral activity in relation to TPU/CuO.

scholarly journals Frequency and Antimicrobial Resistance Patterns of Bacterial Species Isolated from the Body Surface of the Housefly (Musca domestica) in Akure, Ondo State, Nigeria

2020 ◽  
Author(s):  
Babatunde Odetoyin ◽  
Babatunde Adeola ◽  
Olarinde Olaniran
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Species ◽  
Bacterial Load ◽  
The Body ◽  
Resistant Bacteria ◽  
Salmonella Spp ◽  
Isolation Technique ◽  
Garbage Dump ◽  
Antibiotic Susceptibility Test ◽  
Resistance Patterns

Background: The emergence and spread of antibiotic resistant bacteria has become a serious problem worldwide. House­flies are potential carriers of pathogenic and resistant bacteria and could be contributing to the global spread of these strains in the environments.We investigated the prevalence and antimicrobial resistant profiles of bacteria isolated from houseflies in Akure. Methods: Twenty-five houseflies were captured by a sterile nylon net from the slaughterhouse, garbage dump, human house, hospital, and eatery from 9:00am to 1:00pm when the flies were active and transported immediately to the la­bor­atory in sterile containers for processing. Bacterial loads were enumerated by serial dilution and plating on nutrient agar and selective media. Bacteria species were isolated by conventional isolation technique. Antibiotic susceptibility test was determined by the Kirby-Bauer disc diffusion technique. Results: Sixty-seven bacterial species were isolated from 25 samples that were collected. The predominant bacterial species was Escherichia coli (n= 31, 45%), followed by Klebsiella pneumoniae (n= 17, 25%), Staphylococcus aureus (n= 11, 16%) and Pseudomonas aeruginosa (n= 3, 4.3%). The bacterial load of the samples ranged from 9.7×105CFU/mL to 1.65×106CFU/mL. The results revealed that all isolates of Pseudomonas aeruginosa, Salmonella spp, and Proteus mi­rabilis were resistant to streptomycin and cotrimoxazole, augmentin and amoxicillin respectively. None of the S. aureus iso­lates was resistant to cotrimoxazole, chloramphenicol, sparfloxacin, augmentin, and ofloxacin. All isolates were multi-drug resistant. Conclusion: House flies that were collected from the slaughterhouse, garbage dump, human house, hospital, and eatery may participate in the dispersal of pathogenic and resistant bacteria in the study environment.

scholarly journals On the evolutionary ecology of multidrug resistance in bacteria

2017 ◽  
Author(s):  
Sonja Lehtinen ◽  
François Blanquart ◽  
Marc Lipsitch ◽  
Christophe Fraser ◽  
Keyword(s):  
Public Health ◽  
Multidrug Resistance ◽  
Bacterial Species ◽  
Treatment Options ◽  
Antibiotic Sensitivity ◽  
Structural Similarity ◽  
Health Concern ◽  
Resistant Bacteria ◽  
Bacterial Strains ◽  
High Frequencies

AbstractResistance against different antibiotics appears on the same bacterial strains more often than expected by chance, leading to high frequencies of multidrug resistance. There are multiple explanations for this observation, but these tend to be specific to subsets of antibiotics and/or bacterial species, whereas the trend is pervasive. Here, we consider the question in terms of strain ecology: explaining why resistance to different antibiotics is often seen on the same strain requires an understanding of the competition between strains with different resistance profiles. This work builds on models originally proposed to explain another aspect of strain competition: the stable coexistence of antibiotic sensitivity and resistance observed in a number of bacterial species. We first demonstrate a partial structural similarity in these models of coexistence. We then generalise this unified underlying model to multidrug resistance and show that models with this structure predict high levels of association between resistance to different drugs and high multidrug resistance frequencies. We test predictions from this model in six bacterial datasets and find them to be qualitatively consistent with observed trends. The higher than expected frequencies of multidrug resistance are often interpreted as evidence that these strains are out-competing strains with lower resistance multiplicity. Our work provides an alternative explanation that is compatible with long-term stability in resistance frequencies.Author summaryAntibiotic resistance is a serious public health concern, yet the ecology and evolution of drug resistance are not fully understood. This impacts our ability to design effective interventions to combat resistance. From a public health point of view, multidrug resistance is particularly problematic because resistance to different antibiotics is often seen on the same bacterial strains, which leads to high frequencies of multidrug resistance and limits treatment options. This work seeks to explain this trend in terms of strain ecology and the competition between strains with different resistance profiles. Building on recent work exploring why resistant bacteria are not out-competing sensitive bacteria, we show that models originally proposed to explain this observation also predict high multidrug resistance frequencies. These models are therefore a unifying explanation for two pervasive trends in resistance dynamics. In terms of public health, the implication of our results is that new resistances are likeliest to be found on already multidrug resistant strains and that changing patterns of prescription may not be enough to combat multidrug resistance.

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