scholarly journals Environmental free-living amoebae can predate on diverse antibiotic-resistant human pathogens

2021 ◽  
Author(s):  
Félix Bornier ◽  
Eline Zas ◽  
Damien Potheret ◽  
Maria-Halima Laaberki ◽  
Bénédicte Coupat-Goutaland ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Natural Environment ◽  
Rich Source ◽  
Clinical Isolates ◽  
Human Pathogens ◽  
Free Living ◽  
Antibiotic Resistant ◽  
Eukaryotic Microorganisms ◽  
Highly Virulent

We here sought to test the resistance of human pathogens to unaltered environmental free-living amoebae. Amoebae are ubiquitous eukaryotic microorganisms and important predators of bacteria. Environmental amoebae have also been proposed to serve both as potential reservoir and training ground for human pathogens. However, studies addressing their relationship with human pathogens often rely on a few domesticated amoebae selected to feed on rich medium, thereby possibly overestimating the resistance of pathogens to these predatory phagocytes. From an open-air composting site, we recovered over a hundred diverse amoebae able to feed on Acinetobacter baumannii and Klebsiella pneumoniae . In a standardized and quantitative assay for predation, the isolated amoebae showed a broad predation spectrum, killing clinical isolates of A. baumannii , K. pneumoniae , Pseudomonas aeruginosa and Staphylococcus aureus . Interestingly, A. baumannii , previously reported to resist predation by laboratory strains of Acanthamoeba , is efficiently consumed by closely related environmental amoebae. The isolated amoebae are capable of feeding on highly virulent carbapenem-resistant or methicillin-resistant clinical isolates. In conclusion, the natural environment is a rich source of amoebae with broad-spectrum bactericidal activities, including against antibiotic resistant isolates. Importance Free-living amoebae have been proposed to play in important role in hosting and disseminating various human pathogens. The resistance of human pathogens to predation by amoebae is often derived from in vitro experiments using model amoebae. We here sought to isolate environmental amoebae and test their predation on diverse human pathogens, with results that challenge conclusions based on model amoebae. We found that the natural environment is a rich source of diverse amoebae with broad-spectrum predatory activities against human pathogens, including highly virulent and antibiotic resistant clinical isolates.

The relevance of in vitro anthelmintic screening tests employing the free-living stages of trichostrongylid nematodes

1984 ◽  
Vol 58 (2) ◽  
pp. 107-112 ◽  
Author(s):  
O.F. Ibarra ◽  
D.C. Jenkings
Keyword(s):  
Broad Spectrum ◽  
Haemonchus Contortus ◽  
Screening Tests ◽  
Nippostrongylus Brasiliensis ◽  
Good Activity ◽  
Free Living ◽  
Ostertagia Ostertagi ◽  
Nematospiroides Dubius ◽  
Antiparasitic Agents

AbstractThe response of the free-living stages of Nippostrongylus brasiliensis, Nematospiroides dubius, Haemonchus contortus, Trichostrongylus colubriformis and Ostertagia ostertagi to a wide variety of antiparasitic agents in vitro was investigated.All the major broad spectrum veterinary anthelmintics showed good activity against each of these worms with EC30 values varying from about 00002mg/1 for certain benzimidazoles and ivermectin to about 6–5 mg/1 for febantel. Of 22 known narrow spectrum anthelmintics useful only against H. contortus and/or helminths other than trichostrongyles, only 10% showed good activity at concentrations equal to or less than 100mg/1. Further, only one of 15 antiprotozoal agents showed good activity in these tests at the 100mg/1 level.

scholarly journals Joint antibiotic and phage therapy: addressing the limitations of a seemingly ideal phage for treating Staphylococcus aureus infections

2020 ◽  
Author(s):  
Brandon A. Berryhill ◽  
Douglas L. Huseby ◽  
Ingrid C. McCall ◽  
Diarmaid Hughes ◽  
Bruce R. Levin
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Receptor Site ◽  
Clinical Isolates ◽  
Broad Host Range ◽  
Antibiotic Resistant ◽  
Small Colony Variants ◽  
Small Colony

AbstractIn response to increasing frequencies of antibiotic-resistant pathogens, there has been a resurrection of interest in the use of bacteriophage to treat bacterial infections: phage therapy. Here we explore the potential of a seemingly ideal phage, PYOSa, for combination phage and antibiotic treatment of Staphylococcus aureus infections. (i) This K-like phage has a broad host range; all 83 tested clinical isolates of S.aureus tested were susceptible to PYOSa. (ii) Because of the mode of action of PYOSaS. aureus is unlikely to generate classical receptor-site mutants resistant to PYOSa; none were observed in the 13 clinical isolates tested. (iii) PYOSa kills S. aureus at high rates. On the downside, the results of our experiments and tests of the joint action of PYOSa and antibiotics raise issues that must be addressed before PYOSa is employed clinically. Despite the maintenance of the phage, PYOSa does not clear the populations of S. aureus. Due to the ascent of a phenotypically diverse array of small colony variants following an initial demise, the bacterial populations return to densities similar to that of phage-free controls. Using a combination of mathematical modeling and in vitro experiments, we postulate and present evidence for a mechanism to account for the demise–resurrection dynamics of PYOSa and S. aureus. Critically for phage therapy, our experimental results suggest that treatment with PYOSa followed by bactericidal antibiotics can clear populations of S. aureus more effectively than the antibiotics alone.Significance StatementThe increasing frequency of antibiotic-resistant pathogens has fostered a quest for alternative means to treat bacterial infections. Prominent in this quest is a therapy that predates antibiotics: bacteriophage. This study explores the potential of a phage, PYOSa, for treating Staphylococcus aureus infections in combination with antibiotics. On first consideration, this phage, isolated from a commercial therapeutic cocktail, seems ideal for this purpose. The results of this population dynamic and genomic analysis study identify a potential liability of using PYOSa for therapy. Due to the production of potentially pathogenic atypical small colony variants, PYOSa alone cannot eliminate S. aureus populations. However, we demonstrate that by following the administration of PYOSa with bactericidal antibiotics, this limitation and potential liability can be addressed.

scholarly journals In Vitro Activities of the Potent, Broad-Spectrum Carbapenem MK-0826 (L-749,345) against Broad-Spectrum β-Lactamase-and Extended-Spectrum β-Lactamase-Producing Klebsiella pneumoniae and Escherichia coli Clinical Isolates

1999 ◽  
Vol 43 (5) ◽  
pp. 1170-1176 ◽  
Author(s):  
Joyce Kohler ◽  
Karen L. Dorso ◽  
Katherine Young ◽  
Gail G. Hammond ◽  
Hugh Rosen ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Broad Spectrum ◽  
Bacterial Resistance ◽  
Clinical Isolates ◽  
Inoculum Level ◽  
E Coli ◽  
Extended Spectrum ◽  
Group 1

ABSTRACT An important mechanism of bacterial resistance to β-lactam antibiotics is inactivation by β-lactam-hydrolyzing enzymes (β-lactamases). The evolution of the extended-spectrum β-lactamases (ESBLs) is associated with extensive use of β-lactam antibiotics, particularly cephalosporins, and is a serious threat to therapeutic efficacy. ESBLs and broad-spectrum β-lactamases (BDSBLs) are plasmid-mediated class A enzymes produced by gram-negative pathogens, principallyEscherichia coli and Klebsiella pneumoniae. MK-0826 was highly potent against all ESBL- and BDSBL-producingK. pneumoniae and E. coli clinical isolates tested (MIC range, 0.008 to 0.12 μg/ml). In E. coli, this activity was associated with high-affinity binding to penicillin-binding proteins 2 and 3. When the inoculum level was increased 10-fold, increasing the amount of β-lactamase present, the MK-0826 MIC range increased to 0.008 to 1 μg/ml. By comparison, similar observations were made with meropenem while imipenem MICs were usually less affected. Not surprisingly, MIC increases with noncarbapenem β-lactams were generally substantially greater, resulting in resistance in many cases. E. coli strains that produce chromosomal (Bush group 1) β-lactamase served as controls. All three carbapenems were subject to an inoculum effect with the majority of the BDSBL- and ESBL-producers but not the Bush group 1 strains, implying some effect of the plasmid-borne enzymes on potency. Importantly, MK-0826 MICs remained at or below 1 μg/ml under all test conditions.

scholarly journals 728. Activity of Eravacycline Against Contemporary Gram-Negative Clinical Isolates From New York City Hospitals

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S326-S326
Author(s):  
Alejandro Iregui ◽  
Zeb Khan ◽  
David Landman ◽  
John M Quale
Keyword(s):  
New York ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
E Coli ◽  
The Usa ◽  
Recent Collection

Abstract Background Antibiotic-resistant Gram-negative bacteria, including KPC-producing Enterobacteriaceae and carbapenem-resistant A. baumannii, have been problematic hospital pathogens in NYC and other areas. Eravacycline (ERV), a fluorocycline antibiotic released in the USA in 2018, has demonstrated in vitro activity against many of these strains. We tested the activity of ERV against a recent collection of clinical isolates from NYC hospitals. Methods For a 3-month period in 2017, all unique patient isolates of E. coli, K. pneumoniae, Enterobacter spp., and A. baumannii were collected from 7 hospitals in Brooklyn, NY. MICs were performed by broth microdilution for ERV and Tigecycline (TGC) and agar dilution for other antibiotics according to CLSI methodology. Cephalosporin-resistant isolates were screened by PCR for common carbapenemases. Results The susceptibility results for tetracycline and ERV are listed in the Table. Overall, 95% of the Enterobacteriaceae were inhibited by ≤ 0.5 μg/mL of ERV, the FDA-suggested breakpoint. Of 1,876 isolates of E. coli, 4 possessed KPC. ERV MICs for these 4 isolates were 0.125–0.25 μg/mL. Of 518 isolates of K. pneumoniae, 20 possessed KPC. The ERV MIC50 and MIC90 for these isolates were 1 and 1 μg/mL, respectively. Of 172 isolates of Enterobacter spp., 3 possessed KPC. ERV MICs for these 3 isolates were 0.5–1 μg/mL. Of 45 isolates of A. baumannii, 11 isolates possessed a carbapenemase (OXA23 in 8, OXA24 in 2, and KPC in 1). The ERV MIC50 and MIC90 for these isolates were 1 and 2 μg/mL, respectively. Overall, ERV MICs were two-fold lower than TGC MICs for A. baumannii. Conclusion ERV possesses significant in vitro activity against contemporary clinical isolates of Enterobacteriaceae and A. baumannii from NYC, including many carbapenemase producing strains. Disclosures All authors: No reported disclosures.

scholarly journals Scopulariopsis brevicaulis, a Fungal Pathogen Resistant to Broad-Spectrum Antifungal Agents

2003 ◽  
Vol 47 (7) ◽  
pp. 2339-2341 ◽  
Author(s):  
Manuel Cuenca-Estrella ◽  
Alicia Gomez-Lopez ◽  
Emilia Mellado ◽  
Maria J. Buitrago ◽  
Araceli Monzón ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Broad Spectrum ◽  
Fungal Pathogen ◽  
Antifungal Agents ◽  
Antifungal Susceptibility ◽  
Clinical Isolates ◽  
Geometric Means ◽  
Scopulariopsis Brevicaulis

ABSTRACT The antifungal susceptibility results for 32 clinical isolates of Scopulariopsis brevicaulis are presented. Flucytosine and itraconazole were inactive in vitro, and MICs of amphotericin B, voriconazole, and terbinafine for all isolates were high, with geometric means of 13, 25.8, and 14.4 μg/ml, respectively.

scholarly journals In VitroAntimicrobial Activity of Razupenem (SMP-601, PTZ601) against Anaerobic Bacteria

2011 ◽  
Vol 55 (5) ◽  
pp. 2398-2402 ◽  
Author(s):  
Chau Minh Tran ◽  
Kaori Tanaka ◽  
Yuka Yamagishi ◽  
Takatsugu Goto ◽  
Hiroshige Mikamo ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Anaerobic Bacteria ◽  
Clinical Isolates ◽  
Strong Activity ◽  
Content Type ◽  
Spectrum Activity ◽  
Reference Strains ◽  
Gram Positive Cocci ◽  
Broad Spectrum Activity

ABSTRACTWe evaluated thein vitroantianaerobic activity of razupenem (SMP-601, PTZ601), a new parenterally administered carbapenem, against 70 reference strains and 323 clinical isolates. Razupenem exhibited broad-spectrum activity against anaerobes, inhibiting most of the reference strains when used at a concentration of ≤1 μg/ml. Furthermore, it exhibited strong activity, comparable to those of other carbapenems (meropenem and doripenem), against clinically isolated non-fragilis Bacteroidesspp. (MIC90s of 2 μg/ml), with MIC90values of 0.06, 0.03, and 0.5 μg/ml againstPrevotellaspp.,Porphyromonasspp., andFusobacteriumspp., respectively. Clinical isolates of anaerobic Gram-positive cocci,Eggerthellaspp., andClostridiumspp. were highly susceptible to razupenem (MIC90s, 0.03 to 1 μg/ml).

scholarly journals A Murine Model of Mycobacterium kansasii Infection Reproducing Necrotic Lung Pathology Reveals Considerable Heterogeneity in Virulence of Clinical Isolates

2021 ◽  
Vol 12 ◽  
Author(s):  
Vinicius O. Mussi ◽  
Thatiana L. B. V. Simão ◽  
Fabrício M. Almeida ◽  
Edson Machado ◽  
Luciana D. de Carvalho ◽  
...  
Keyword(s):  
Lung Disease ◽  
Pulmonary Disease ◽  
Virulent Strain ◽  
The United States ◽  
Clinical Isolates ◽  
Lung Pathology ◽  
Mycobacterium Kansasii ◽  
Considerable Heterogeneity ◽  
Highly Virulent

Among non-tuberculous mycobacteria, Mycobacterium kansasii is one of the most pathogenic, able to cause pulmonary disease indistinguishable from tuberculosis in immunocompetent susceptible adults. The lack of animal models that reproduce human-like lung disease, associated with the necrotic lung pathology, impairs studies of M. kansasii virulence and pathogenicity. In this study, we examined the ability of the C57BL/6 mice, intratracheally infected with highly virulent M. kansasii strains, to produce a chronic infection and necrotic lung pathology. As a first approach, we evaluated ten M. kansasii strains isolated from Brazilian patients with pulmonary disease and the reference strain M. kansasii ATCC 12478 for virulence-associated features in macrophages infected in vitro; five of these strains differing in virulence were selected for in vivo analysis. Highly virulent isolates induced progressive lung disease in mice, forming large encapsulated caseous granulomas in later stages (120–150 days post-infection), while the low-virulent strain was cleared from the lungs by day 40. Two strains demonstrated increased virulence, causing premature death in the infected animals. These data demonstrate that C57BL/6 mice are an excellent candidate to investigate the virulence of M. kansasii isolates. We observed considerable heterogeneity in the virulence profile of these strains, in which the presence of highly virulent strains allowed us to establish a clinically relevant animal model. Comparing public genomic data between Brazilian isolates and isolates from other geographic regions worldwide demonstrated that at least some of the highly pathogenic strains isolated in Brazil display remarkable genomic similarities with the ATCC strain 12478 isolated in the United States 70 years ago (less than 100 SNPs of difference), as well as with some recent European clinical isolates. These data suggest that few pathogenic clones have been widely spread within M. kansasii population around the world.

Sign in / Sign up

Export Citation Format

Share Document