Examining the safety of respiratory and intravenous inoculation of Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus in a mouse model (original) (raw)
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Effect of Predatory Bacteria on Human Cell Lines
PloS one, 2016
Predatory bacteria are Gram-negative bacteria that prey on other Gram-negative bacteria and have been considered as potential therapeutic agents against multi-drug resistant pathogens. In vivo animal models have demonstrated that predatory bacteria are non-toxic and non-immunogenic in rodents. In order to consider the use of predatory bacteria as live antibiotics, it is important to investigate their effect on human cells. The aim of this study was to determine the effect of Bdellovibrio bacteriovorus strains 109J and HD100, and Micavibrio aeruginosavorus strain ARL-13 on cell viability and inflammatory responses of five human cell lines, representative of clinically relevant tissues. We found that the predators were not cytotoxic to any of the human cell lines tested. Microscopic imaging showed no signs of cell detachment, as compared to predator-free cells. In comparison to an E. coli control, exposure to higher concentrations of the predators did not trigger a significant elevati...
Scientific Reports
Rob till, patrick J. tighe, sally p. Wheatley, Luisa Martinez-pomares, R. elizabeth sockett & Jess tyson In assessing the potential of predatory bacteria, such as Bdellovibrio bacteriovorus, to become live therapeutic agents against bacterial infections, it is crucial to understand and quantify Bdellovibrio host cell interactions at a molecular level. Here, we quantify the interactions of live B. bacteriovorus with human phagocytic cells, determining the uptake mechanisms, persistence, associated cytokine responses and intracellular trafficking of the non-growing B. bacteriovorus in PMA-differentiated U937 cells. B. bacteriovorus are engulfed by U937 cells and persist for 24 h without affecting host cell viability and can be observed microscopically and recovered and cultured post-uptake. the uptake of predators is passive and depends on the dynamics of the host cell cytoskeleton; the engulfed predators are eventually trafficked through the phagolysosomal pathway of degradation. We have also studied the prevalence of B. bacteriovorus specific antibodies in the general human population. Together, these results quantify a period of viable persistence and the ultimate fate of B. bacteriovorus inside phagocytic cells. they provide new knowledge on predator availability inside hosts, plus potential longevity and therefore potential efficacy as a treatment in humans and open up future fields of work testing if predators can prey on host-engulfed pathogenic bacteria. In response to the emergence of antimicrobial-resistant bacterial infections as a global health issue, several alternative, non-small molecule measures, are being sought to treat drug resistant bacterial infections 1-4. One such approach is the potential use of living predatory bacteria such as Bdellovibrio bacteriovorus 4-7 , a Gram-negative predatory bacterium, which invades and preys upon a wide range of Gram-negative bacteria in their natural environments that are soil and water 6. In in vitro conditions, B. bacteriovorus can prey upon and kill several Gram-negative pathogenic bacteria, irrespective of their antibiotic resistance profile 8 and more recently, the susceptibility of these pathogens to predation has been shown in vivo 9-11. Recent studies have verified the apparent safety of predators using in vitro cell culture 12-14 and in vivo animal models 9-11,14-18. The questions that remain to be addressed are with regard to their interactions as living, but seemingly non-pathogenic bacteria, with the host immune system, which involves evaluation of the mechanisms of uptake and persistence of predatory bacteria within phagocytes and the processes involved in their clearance from these host cells. Also it is not known how frequently the human immune system encounters predatory bacteria in normal life. All microorganisms , including bacterial pathogens, encounter professional phagocytic cells such as macrophages and dendritic cells which are the first line of defence and the essential components of the innate immune system 19,20. These host cells engulf and ingest internalised microorganisms through phagocytosis, a process driven by receptor-ligand interactions resulting in cytoskeletal remodelling and engulfment of targets by pseudopods. Phagocytosis culminates in the formation of sealed intracellular compartments, namely, phagosomes
Bdellovibrio bacteriovorus: More than Just a Bacterial Hunter
Postępy Mikrobiologii - Advancements of Microbiology
Bdellovibrio bacteriovorus is a predatory gram-negative delta-proteobacteria that preys on other gram-negative bacterial species. With the surge in the cases of Anti-Microbial Resistance and the demand to replace conventional antibiotics, this predatory attribute of B. bacteriovorus has led to a vast number of studies in the last decade alone. These studies demonstrated various aspects of predation and proposed using B. bacteriovorus as an alternative new approach to conventional antibiotics in humans. Here we review the current progress made in this promising new area of research to develop novel antibacterial approaches.
Predatory Bacteria: A Potential Ally against Multidrug-Resistant Gram-Negative Pathogens
Plos One, 2013
Multidrug-resistant (MDR) Gram-negative bacteria have emerged as a serious threat to human and animal health. Bdellovibrio spp. and Micavibrio spp. are Gram-negative bacteria that prey on other Gram-negative bacteria. In this study, the ability of Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus to prey on MDR Gram-negative clinical strains was examined. Although the potential use of predatory bacteria to attack MDR pathogens has been suggested, the data supporting these claims is lacking. By conducting predation experiments we have established that predatory bacteria have the capacity to attack clinical strains of a variety of ß-lactamase-producing, MDR Gram-negative bacteria. Our observations indicate that predatory bacteria maintained their ability to prey on MDR bacteria regardless of their antimicrobial resistance, hence, might be used as therapeutic agents where other antimicrobial drugs fail.
Effect of predatory bacteria on the gut bacterial microbiota in rats
Scientific reports, 2017
Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus are Gram-negative proteobacteria that are obligate predators of other Gram-negative bacteria and are considered potential alternatives to antibiotics. Most studies focusing on predatory bacteria have been performed in vitro, thus the effect of predatory bacteria on a live host, including the impact on the ecology of the native microbiota, has yet to be fully examined. In this study, intrarectal inoculations of Sprague-Dawley rats with predatory bacteria were performed. Additionally, feces were collected for seven days post-inoculation to determine the effect on gut bacterial diversity. Rat colonic tissue exhibited no abnormal histopathological effects due to predatory bacteria. A modest increase in pro-inflammatory cytokines was measured in the colons of rats inoculated with predatory bacteria by 24 and 48 hours, with all but IL-13 returning to baseline by seven days. V4 16S rRNA gene sequencing of fecal DNA demonstrated mini...
2020
Background & Objectives: Bdellovibrio-and-like organisms (BALOs) are a group of predatory bacteria which invade other Gram-negative bacterial cells for growth. The bacteriolytic nature of Bdellovibrios makes them one of the promising alternatives for conventional antibiotics. In this study, the isolation and molecular identification of Bdellovibrio bacteriovorus strain SOIR-1 was described. The antibiotic resistance pattern of some clinically isolated Gram-negative pathogens was determined, and the predatory potency of SOIR-1 toward them was evaluated. Material & Methods: Double-layer agar technique, transmission electron microscopy, and PCR targeting the Bdellovibrios-specific hit locus were used for the isolation, morphological investigation, and molecular identification of SOIR-1, respectively. Following the antibiotic resistance profile determination of clinical isolates, the bacteriolytic activity of SOIR-1 against them was evaluated through the plaque formation assay and lysis...
Scientific Reports
This work aimed to evaluate the predatory activity of Bdellovibrio bacteriovorus 109J on clinical isolates of Pseudomonas aeruginosa selected from well-characterized collections of cystic fibrosis (CF) lung colonization (n = 30) and bloodstream infections (BSI) (n = 48) including strains selected by genetic lineage (frequent and rare sequence types), antibiotic resistance phenotype (susceptible and multidrug-resistant isolates), and colony phenotype (mucoid and non-mucoid isolates). The intraspecies predation range (I-PR) was defined as the proportion of susceptible strains within the entire collection. In contrast, the predation efficiency (PE) is the ratio of viable prey cells remaining after predation compared to the initial inoculum. I-PR was significantly higher for CF (67%) than for BSI P. aeruginosa isolates (35%) probably related to an environmental origin of CF strains whereas invasive strains are more adapted to humans. I-PR correlation with bacterial features such as muco...
Environmental predators as models for bacterial pathogenesis
Environmental Microbiology, 2007
Environmental bacteria are constantly threatened by bacterivorous predators such as free-living protozoa and nematodes. In the course of their coevolution with environmental predators, some bacteria developed sophisticated defence mechanisms, including the secretion of toxins, or the capacity to avoid lysosomal killing and to replicate intracellularly within protozoa. To analyse the interactions with bacterial pathogens on a molecular, cellular or organismic level, protozoa and other non-mammalian hosts are increasingly used. These include amoebae, as well as genetically tractable hosts, such as the social amoeba Dictyostelium discoideum, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Using these hosts, the virulence mechanisms of opportunistic pathogenic bacteria such as Legionella, Mycobacterium, Pseudomonas or Vibrio were found to be not only relevant for the interactions of the bacteria with protozoa, nematodes and insect phagocytes, but also with mammalian hosts including humans. Thus, non-mammalian model hosts provide valuable insight into the pathogenesis of environmental bacteria.