scholarly journals Galleria mellonella as a Suitable Model of Bacterial Infection: Past, Present and Future

2021 ◽  
Vol 11 ◽  
Author(s):  
Guillaume Ménard ◽  
Astrid Rouillon ◽  
Vincent Cattoir ◽  
Pierre-Yves Donnio
Keyword(s):  
Pathogenic Bacteria ◽  
Galleria Mellonella ◽  
Current Knowledge ◽  
Infection Model ◽  
Suitable Model ◽  
Ethical Aspects ◽  
Robust Model ◽  
Conventional Animal ◽  
Per Se ◽  
Microbiological Aspects

The increasing interest for Galleria mellonella larvae as an infection model is evidenced by the number of papers reporting its use, which increases exponentially since the early 2010s. This popularity was initially linked to limitation of conventional animal models due to financial, technical and ethical aspects. In comparison, alternative models (e.g. models using Caenorhabditis elegans, Drosophila melanogaster or G. mellonella) were cheap, simple to use and not limited by ethical regulation. Since then, similar results have been established with G. mellonella model comparatively to vertebrates, and it is more and more often used as a robust model per se, not only as an alternative to the murine model. This review attempts to summarize the current knowledge supporting the development of this model, both on immunological and microbiological aspects. For that, we focus on investigation of virulence and new therapies for the most important pathogenic bacteria. We also discuss points out directions for standardization, as well as recent advances and new perspectives for monitoring host-pathogen interactions.

Inhibitory effect of biofilm-forming Lactobacillus kunkeei strains against virulent Pseudomonas aeruginosa in vitro and in honeycomb moth (Galleria mellonella) infection model

2018 ◽  
Vol 9 (2) ◽  
pp. 257-268 ◽  
Author(s):  
P. Berríos ◽  
J.A. Fuentes ◽  
D. Salas ◽  
A. Carreño ◽  
P. Aldea ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Biofilm Formation ◽  
Pathogenic Bacteria ◽  
Galleria Mellonella ◽  
Wide Spectrum ◽  
Inhibitory Effect ◽  
Lactobacillus Species ◽  
Infection Model ◽  
Lactobacillus Kunkeei

Biofilms correspond to complex communities of microorganisms embedded in an extracellular polymeric matrix. Biofilm lifestyle predominates in Pseudomonas aeruginosa, an opportunistic Gram negative pathogen responsible for a wide spectrum of infections in humans, plants and animals. In this context, anti-biofilm can be considered a key strategy to control P. aeruginosa infections, thereby more research in the field is required. On the other hand, Lactobacillus species have been described as beneficial due to their anti-biofilm properties and their consequent effect against a wide spectrum of pathogens. In fact, biofilm-forming Lactobacilli seem to be more efficient than their planktonic counterpart to antagonise pathogenic bacteria. In this work, we demonstrated that Lactobacillus kunkeei, a novel Lactobacillus species isolated from honeybee guts, can form biofilms in vitro. In addition, the L. kunkeei biofilm can, in turn, inhibit the formation of P. aeruginosa biofilms. Finally, we found that L. kunkeei strains attenuate infection of P. aeruginosa in the Galleria mellonella model, presumably by affecting P. aeruginosa biofilm formation and/or their stability. Since L. kunkeei presents characteristics of a probiotic, this work provides evidence arguing that the use of this Lactobacillus species in both animals (including insects) and humans could contribute to impair P. aeruginosa biofilm formation.

scholarly journals Phage Resistance Is Associated with Decreased Virulence in KPC-Producing Klebsiella pneumoniae of the Clonal Group 258 Clade II Lineage

2021 ◽  
Vol 9 (4) ◽  
pp. 762
Author(s):  
Lucia Henrici De Angelis ◽  
Noemi Poerio ◽  
Vincenzo Di Pilato ◽  
Federica De Santis ◽  
Alberto Antonelli ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Parental Strain ◽  
Bacterial Infections ◽  
Capsular Polysaccharide ◽  
Galleria Mellonella ◽  
Bacterial Pathogen ◽  
Phage Resistance ◽  
Infection Model ◽  
Lytic Phage ◽  
Susceptible Host

Phage therapy is now reconsidered with interest in the treatment of bacterial infections. A major piece of information for this application is the definition of the molecular targets exploited by phages to infect bacteria. Here, the genetic basis of resistance to the lytic phage φBO1E by its susceptible host Klebsiella pneumoniae KKBO-1 has been investigated. KKBO-1 phage-resistant mutants were obtained by infection at high multiplicity. One mutant, designated BO-FR-1, was selected for subsequent experiments, including virulence assessment in a Galleria mellonella infection model and characterization by whole-genome sequencing. Infection with BO-FR-1 was associated with a significantly lower mortality when compared to that of the parental strain. The BO-FR-1 genome differed from KKBO-1 by a single nonsense mutation into the wbaP gene, which encodes a glycosyltransferase involved in the first step of the biosynthesis of the capsular polysaccharide (CPS). Phage susceptibility was restored when BO-FR-1 was complemented with the constitutive wbaP gene. Our results demonstrated that φBO1E infects KKBO-1 targeting the bacterial CPS. Interestingly, BO-FR-1 was less virulent than the parental strain, suggesting that in the context of the interplay among phage, bacterial pathogen and host, the emergence of phage resistance may be beneficial for the host.

scholarly journals Designing P. aeruginosa synthetic phages with reduced genomes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Diana P. Pires ◽  
Rodrigo Monteiro ◽  
Dalila Mil-Homens ◽  
Arsénio Fialho ◽  
Timothy K. Lu ◽  
...  
Keyword(s):  
Galleria Mellonella ◽  
Antibacterial Properties ◽  
Genetically Engineered ◽  
In Vivo Studies ◽  
Infection Model ◽  
Promising Therapeutic Approach ◽  
Genes Encoding ◽  
First Time

AbstractIn the era where antibiotic resistance is considered one of the major worldwide concerns, bacteriophages have emerged as a promising therapeutic approach to deal with this problem. Genetically engineered bacteriophages can enable enhanced anti-bacterial functionalities, but require cloning additional genes into the phage genomes, which might be challenging due to the DNA encapsulation capacity of a phage. To tackle this issue, we designed and assembled for the first time synthetic phages with smaller genomes by knocking out up to 48% of the genes encoding hypothetical proteins from the genome of the newly isolated Pseudomonas aeruginosa phage vB_PaeP_PE3. The antibacterial efficacy of the wild-type and the synthetic phages was assessed in vitro as well as in vivo using a Galleria mellonella infection model. Overall, both in vitro and in vivo studies revealed that the knock-outs made in phage genome do not impair the antibacterial properties of the synthetic phages, indicating that this could be a good strategy to clear space from phage genomes in order to enable the introduction of other genes of interest that can potentiate the future treatment of P. aeruginosa infections.

scholarly journals Interactions between Rainbow Trout Eyed Eggs and Flavobacterium spp. Using a Bath Challenge Model: Preliminary Evaluation of Bacteriophages as Pathogen Control Agents

2021 ◽  
Vol 9 (5) ◽  
pp. 971
Author(s):  
Valentina L. Donati ◽  
Inger Dalsgaard ◽  
Anniina Runtuvuori-Salmela ◽  
Heidi Kunttu ◽  
Johanna Jørgensen ◽  
...  
Keyword(s):  
Rainbow Trout ◽  
Pathogenic Bacteria ◽  
Infection Model ◽  
Preliminary Evaluation ◽  
Fish Eggs ◽  
Short Term ◽  
Rainbow Trout Oncorhynchus Mykiss ◽  
Pathogen Control ◽  
Number Of Bacteria ◽  
Bath Challenge

The microbial community surrounding fish eyed eggs can harbor pathogenic bacteria. In this study we focused on rainbow trout (Oncorhynchus mykiss) eyed eggs and the potential of bacteriophages against the pathogenic bacteria Flavobacterium psychrophilum and F. columnare. An infection bath method was first established, and the effects of singular phages on fish eggs was assessed (survival of eyed eggs, interaction of phages with eyed eggs). Subsequently, bacteria-challenged eyed eggs were exposed to phages to evaluate their effects in controlling the bacterial population. Culture-based methods were used to enumerate the number of bacteria and/or phages associated with eyed eggs and in the surrounding environment. The results of the study showed that, with our infection model, it was possible to re-isolate F. psychrophilum associated with eyed eggs after the infection procedure, without affecting the survival of the eggs in the short term. However, this was not possible for F. columnare, as this bacterium grows at higher temperatures than the ones recommended for incubation of rainbow trout eyed eggs. Bacteriophages do not appear to negatively affect the survival of rainbow trout eyed eggs and they do not seem to strongly adhere to the surface of eyed eggs either. Finally, the results demonstrated a strong potential for short term (24 h) phage control of F. psychrophilum. However, further studies are needed to explore if phage control can be maintained for a longer period and to further elucidate the mechanisms of interactions between Flavobacteria and their phages in association with fish eggs.

Emergence of ceftazidime/avibactam resistance in KPC-3-producing Klebsiella pneumoniae in vivo

2019 ◽  
Vol 74 (11) ◽  
pp. 3211-3216 ◽  
Author(s):  
Stephan Göttig ◽  
Denia Frank ◽  
Eleonora Mungo ◽  
Anika Nolte ◽  
Michael Hogardt ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Klebsiella Pneumoniae ◽  
Selection Pressure ◽  
Galleria Mellonella ◽  
Phenotypic Characterization ◽  
Infection Model ◽  
Development Of Resistance ◽  
Time Kill

Abstract Objectives The β-lactam/β-lactamase inhibitor combination ceftazidime/avibactam is active against KPC-producing Enterobacterales. Herein, we present molecular and phenotypic characterization of ceftazidime/avibactam resistance in KPC-3-producing Klebsiella pneumoniae that emerged in vivo and in vitro. Methods Sequence analysis of blaKPC-3 was performed from clinical and in vitro-generated ceftazidime/avibactam-resistant K. pneumoniae isolates. Time–kill kinetics and the Galleria mellonella infection model were applied to evaluate the activity of ceftazidime/avibactam and imipenem alone and in combination. Results The ceftazidime/avibactam-resistant clinical K. pneumoniae isolate revealed the amino acid change D179Y in KPC-3. Sixteen novel mutational changes in KPC-3 among in vitro-selected ceftazidime/avibactam-resistant isolates were described. Time–kill kinetics showed the emergence of a resistant subpopulation under selection pressure with either imipenem or ceftazidime/avibactam. However, combined selection pressure with imipenem plus ceftazidime/avibactam prevented the development of resistance and resulted in bactericidal activity. Concordantly, the G. mellonella infection model revealed that monotherapy with ceftazidime/avibactam is prone to select for resistance in vivo and that combination therapy with imipenem results in significantly better survival. Conclusions Ceftazidime/avibactam is a valuable antibiotic against MDR and carbapenem-resistant Enterobacterales. Based on time–kill kinetics as well as an in vivo infection model we postulate a combination therapy of ceftazidime/avibactam and imipenem as a strategy to prevent the development of ceftazidime/avibactam resistance in KPC-producing Enterobacterales in vivo.

Insects as vectors of foodborne pathogenic bacteria

2011 ◽  
Vol 4 (1) ◽  
pp. 5-16 ◽  
Author(s):  
Jeffrey Blazar ◽  
Marc Allard ◽  
E. Kurt Lienau
Keyword(s):  
Food Safety ◽  
Foodborne Pathogens ◽  
Pathogenic Bacteria ◽  
Current Knowledge ◽  
Disease Outbreaks ◽  
House Fly ◽  
American Cockroach ◽  
Health Concern ◽  
Foodborne Disease ◽  
Salmonella Spp

AbstractFood safety is an important consideration worldwide. To maintain and improve our current knowledge of foodborne disease outbreaks, we must understand some of the more imminent issues related to food safety. A variety of agents are responsible for transmitting the estimated 76 million cases of illnesses caused by foodborne pathogens every year. This review explores why insects pose a serious health concern, in terms of worldwide food safety initiatives, by looking at evidence in published <abs>Food safety is an important consideration worldwide. To maintain and improve our current knowledge of foodborne disease outbreaks, we must understand some of the more imminent issues related to food safety. A variety of agents are responsible for transmitting the estimated 76 million cases of illnesses caused by foodborne pathogens every year. This review explores why insects pose a serious health concern, in terms of worldwide food safety initiatives, by looking at evidence in published literature. We highlight at least eleven different species of insects, including the lesser mealworm, Alphitobius diaperinus (Panzer); secondary screwworm, Cochliomyia macellaria (Fabricius); synanthropic flies [flesh fly, Sarcophaga carnaria (L.); house fly, Musca domestica (L.); fruit fly, Drosophila melanogaster (Meigen); and stable fly, Stomoxys calcitrans (L.)], American cockroach, Periplaneta americana (L.); German cockroach, Blatella germanica (L.); Oriental cockroach, Blatta orientalis (L.); Pacific beetle cockroach, Diploptera punctata (Eschscholtz); and Speckled feeder cockroach, Nauphoeta cinerea (Olivier), which act as vectors for Salmonella spp. or Escherichia coli and illustrate how these insects are successful vectors of foodborne disease outbreaks. We propose that insects be considered as one of the latest issues in food safety initiatives. Not only are some insects extremely important contributors to diseases, but now we suggest that more research into insects as potential carriers of E. coli and Salmonella spp., and therefore as contributing to foodborne disease outbreaks, is granted.

scholarly journals How to Train Your Phage: The Recent Efforts in Phage Training

Biologics ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 70-88
Author(s):  
Abdallah Abdelsattar ◽  
Alyaa Dawooud ◽  
Nouran Rezk ◽  
Salsabil Makky ◽  
Anan Safwat ◽  
...  
Keyword(s):  
Host Range ◽  
Pathogenic Bacteria ◽  
Bacterial Resistance ◽  
Phage Therapy ◽  
Current Knowledge ◽  
Lytic Replication ◽  
Resistant Bacteria ◽  
Infection Cycles ◽  
Different Strains ◽  
Specific Species

Control of pathogenic bacteria by deliberate application of predatory phages has potential as a powerful therapy against antibiotic-resistant bacteria. The key advantages of phage biocontrol over antibacterial chemotherapy are: (1) an ability to self-propagate inside host bacteria, (2) targeted predation of specific species or strains of bacteria, (3) adaptive molecular machinery to overcome resistance in target bacteria. However, realizing the potential of phage biocontrol is dependent on harnessing or adapting these responses, as many phage species switch between lytic infection cycles (resulting in lysis) and lysogenic infection cycles (resulting in genomic integration) that increase the likelihood of survival of the phage in response to external stress or host depletion. Similarly, host range will need to be optimized to make phage therapy medically viable whilst avoiding the potential for deleteriously disturbing the commensal microbiota. Phage training is a new approach to produce efficient phages by capitalizing on the evolved response of wild-type phages to bacterial resistance. Here we will review recent studies reporting successful trials of training different strains of phages to switch into lytic replication mode, overcome bacterial resistance, and increase their host range. This review will also highlight the current knowledge of phage training and future implications in phage applications and phage therapy and summarize the recent pipeline of the magistral preparation to produce a customized phage for clinical trials and medical applications.

scholarly journals Amycomicin is a potent and specific antibiotic discovered with a targeted interaction screen

2018 ◽  
Vol 115 (40) ◽  
pp. 10124-10129 ◽  
Author(s):  
Gleb Pishchany ◽  
Emily Mevers ◽  
Sula Ndousse-Fetter ◽  
Dennis J. Horvath ◽  
Camila R. Paludo ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Pathogenic Bacteria ◽  
Fatty Acid Biosynthesis ◽  
Streptomyces Coelicolor ◽  
Specific Inhibitor ◽  
Mouse Skin ◽  
Infection Model ◽  
Microbial Species ◽  
Rdna Sequencing ◽  
New Antibiotics

The rapid emergence of antibiotic-resistant pathogenic bacteria has accelerated the search for new antibiotics. Many clinically used antibacterials were discovered through culturing a single microbial species under nutrient-rich conditions, but in the environment, bacteria constantly encounter poor nutrient conditions and interact with neighboring microbial species. In an effort to recapitulate this environment, we generated a nine-strain actinomycete community and used 16S rDNA sequencing to deconvolute the stochastic production of antimicrobial activity that was not observed from any of the axenic cultures. We subsequently simplified the community to just two strains and identifiedAmycolatopsissp. AA4 as the producing strain andStreptomyces coelicolorM145 as an inducing strain. Bioassay-guided isolation identified amycomicin (AMY), a highly modified fatty acid containing an epoxide isonitrile warhead as a potent and specific inhibitor ofStaphylococcus aureus. Amycomicin targets an essential enzyme (FabH) in fatty acid biosynthesis and reducesS. aureusinfection in a mouse skin-infection model. The discovery of AMY demonstrates the utility of screening complex communities against specific targets to discover small-molecule antibiotics.

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