Source: KANSAS STATE UNIV submitted to
MICROBIAL ECOLOGY AND MEDICAL SIGNIFICANCE OF HOUSE FLIES
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
0204286
Grant No.
2005-35302-16340
Cumulative Award Amt.
(N/A)
Proposal No.
2005-00893
Multistate No.
(N/A)
Project Start Date
Sep 1, 2005
Project End Date
Aug 31, 2008
Grant Year
2005
Program Code
[51.2]- (N/A)
Recipient Organization
KANSAS STATE UNIV
(N/A)
MANHATTAN,KS 66506
Performing Department
ENTOMOLOGY
Non Technical Summary
House flies (HF) develop in the manure of domestic animals including those that are frequently fed antibiotics for growth promotion and prophylaxis. In the United States, due to heavy use of antimicrobial agents in the agriculture, antibiotic resistance genes in the gastro-intestinal microbial communities of domestic animals and their feces/manure have become common. Antibiotic resistance in clinical isolates has become a serious problem because of the limited number of effective antibiotics available for treatment of human bacterial infections. The connection between antibiotic resistances of food animal origin and that of clinical isolates has been suggested in several studies; however, the ecology of bacterial antibiotic resistance and virulence genes in the environment is poorly understood. Due to their developmental habitats, mode of feeding, unrestricted movement, and attraction to residential areas, the manure-borne insects, primarily HF, likely play an important role in the ecology and dissemination of virulence and antibiotic resistance genes in agricultural and urban environment. To assess this role, enterococci have been chosen as a bacterial model system because of their medical importance (virulence factors), frequent and diverse antibiotic resistance genes, great variety of mobile genetic elements (pheromone responsive plasmids, conjugative plasmids, transposons), and their consistent presence in animal and human feces as well as in the digestive tract of manure-borne flies.
Animal Health Component
(N/A)
Research Effort Categories
Basic
100%
Applied
(N/A)
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
31231201130100%
Goals / Objectives
1) Assessment of the antibiotic resistance profiles of enterococci from the gastro-intestinal community of adult house flies associated with the manure of animals frequently exposed to antibiotics (feedlot cattle) and animals with no or very limited exposure to antibiotics (American bison) 2) Characterization of selected enterococcal isolates from manure and flies by: a) Assessment of the diversity of tetracycline, vancomycin, and erythromycin resistance genes b) Screening for virulence factors including, cytolysin (cylA, cylB), gelatinase (gelE) and selected adhesins (as, esp).
Project Methods
Fresh fecal material of feedlot cattle (K-State Agricultural Experimental Station) and American bison (Konza Prairie Biological Station) and associated adults of HF will be collected three times per year (spring, summer, fall) for two consecutive years. Feedlot cattle receive tylosin and monensin as growth promoters 120 days before slaughter and oxytetracycline, ceftiofur (cephalosporin), and tilmycosin (fluoronquinolone) therapeutically. The herd of American bison has not received any antibiotics for the past 10 years. Ten grams of fecal material from each sample will be mixed in 50 ml of PBS buffer and serially diluted. Adult flies will be identified under the dissection microscope and fifty randomly selected HF from each collection time will be used for the bacterial analysis. Flies will be surface sterilized by sodium hypochlorite and ethanol and individually homogenized in 5 ml of PBS and the homogenate serially diluted. Serially diluted samples in PBS (to 10-8) will be drop plated in triplicates on mENT agar. The plates will be cultured aerobically at 37oC for 48 hours. Red, burgundy, and pink colonies will be counted using a colony counter to assess the enterococcal population size in each sample. Five colonies will be randomly selected from each sample, streaked on TSBA and stored at 4oC until further analysis. The genus level will be confirmed phenotypically. Isolates will be identified identified to species level by multiplex using species-specific primers. A customized 96 well panel of antimicrobials for the NARMS program will be used for antibiotic resistance testing. Results will be interpreted according to NCCLS guidelines. Antibiotics selected for this study include: ampicillin, penicillin, high level-gentamicin, high-level streptomycin, vancomycin, teicoplanin, erythromycin, lincomycin, virginiamycin, quinopristin/dalfopristin, tetracycline, chloramphenicol, neomycin, norfloxacin, nitrofurantoin, levofloxacin and ciprofloxacin. A comparable resistance profile between ruminant and fly populations can be an indicator of strain transfer between mammals and flies and/or vice versa. Resistance genes to tetracycline [tet (O), tet(S), tet (W), tet (Q), tet (K), tet (C), tet (L)]; to erythromycin [erm (A), erm (B), erm (C) ], and vancomycin [van (A), and van (B)] will detected by specific PCR primers. Detection of genes of five virulence factors, including cylA, cylB, as, esp, and gelE will be performed using multiplex PCR.

Progress 09/01/05 to 08/31/08

Outputs
OUTPUTS: Previously, we have shown that house flies (HF) in fast-food restaurants commonly carry antibiotic resistant and potentially virulent enterococci. In this study, the potential of field collected house flies to contaminate ready-to-eat-food (RTEF) with enterococci was assessed by laboratory bioassays. House flies were collected with a sweep net in a cattle feedlot and exposed to a beef patty for 0.5, 1.0, 3.0, and 24 hours. The exposure of RTEF to flies resulted in 100% contamination with enterococci in all bioassays regardless of the number of HF and the length of the exposure time. Even a short-time exposure (0.5 hour) with 5 HF resulted in heavy food contamination. Phenotypic screening showed that E. faecalis (the dominant species) in RTEF were resistant to ciprofloxacin (17.4%), tetracycline (13.0%), erythromycin (13.0%), and chloramphenicol (4.3%). This study demonstrates a great potential of HF from a cattle feedlot to contaminate RTEF with enterococci in a short period of time. In another study, the influx of enterococcal antibiotic resistance (AR) and virulence genes from RTEF to the human digestive tract was assessed. Three RTEFs (chicken salad, chicken burger, carrot cake) were sampled from five fast-food restaurants five-times in summer and winter. The prevalence of enterococci was significantly higher in summer (92.0% salad and 64.0% burger) when HF are commonly present than in winter (64.0% salad and 24.0% burger). The overall concentration of enterococci during both seasons was similar; the most prevalent were Enterococcus casseliflavus and E. hirae in winter (WI), and E. faecium, E. casseliflavus, and E. faecalis in summer (SU). Resistance in WI was detected primarily to tetracycline, ciprofloxacin, and erythromycin. Summer isolates were mainly resistant to tetracycline, erythromycin, and kanamycin. The most common tet-gene was tet(M). The prevalence of virulence genes was low. Genotyping of E. faecalis and E. faecium using pulsed-field gel electrophoresis revealed that the food contamination likely originated from various sources and it was not clonal. Our conservative estimate for the influx of tet-genes alone to the human digestive tract is 3.8 x 105 per meal (chicken salad). This AR gene influx is frequent because RTEF are commonly consumed and that may play a role in the acquisition of AR determinants in the human digestive tract. We also continue to work on the bison and cattle isolates to determine the potential source of antibiotic resistance in the Konza Prairie bison. We have begun to characterize enterococci strains by multi-locus sequence typing (MLST; for E. faecalis and E. faecium isolates) and by PFGE. These methods will help us to detect any clonal spread in the local environment. To account for the high likelihood that horizontal gene transfer mediated by mobile genetic elements such as plasmids and transposons plays a role, we have started to characterize plasmids harbored in the isolates obtained from cattle and bison. Preliminary results indicate identical restriction fragment pattern in at least one plasmid originating from isolates found in cattle and bison. PARTICIPANTS: Helmut Hirt, Asst. Professor, Biology, K-State (Co-PI); Lilia Macovei, Postdoctoral Research Associate, K-State, Entomology; Mastura Akhtar, Graduate student (Ph.D.), K-State, Entomology TARGET AUDIENCES: Kansas farmers and ranchers, restaurant management personnel, pest control operators, microbial ecologists, clinicians, general public PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
The ecology of antibiotic resistance and virulence genes in the environment is not well understood. In these studies, we have shown that ready-to-eat food is frequently contaminated with antibiotic resistant and potentially virulent enterococci. Antibiotic resistance genes in these bacteria are on mobile genetic elements and can be transferred to bacteria in human digestive tract. One of the potential sources of food contamination is house flies. A small number of wild house flies (commonly present in residential areas in summer) have a great potential to contaminate food with antibiotic resistant enterococci in a short time. The bison population at Konza prairie can serve as a sentinel population (no antibiotic exposure) to study the spread and origin of antibiotic resistance.

Publications

  • Macovei, L. and L. Zurek* (2007). Influx of enterococci and associated antibiotic resistance and virulence genes from ready-to-eat food to the human digestive tract. Applied and Environmental Microbiology 73: 6740-6747.
  • Macovei, L., B. Miles, and L. Zurek* (2007). The potential of house flies to contaminate ready-to-eat food with antibiotic resistant enterococci. Journal of Food Protection (in press).


Progress 09/01/06 to 09/01/07

Outputs
Enterococci from the digestive tract of 260 house flies (Musca domestica L.) collected from five restaurants were characterized. House flies frequently (97% positive flies) carried enterococci (mean: 3.1x103 CFU/fly). Using multiplex-PCR, 205 out of 355 randomly selected enterococcal isolates were identified and characterized. The majority represented Enterococcus faecalis (88.2%), followed by E. faecium (6.8%), and E. casseliflavus (4.9%). E. faecalis was phenotypically resistant to tetracycline (66.3%), erythromycin (23.8%), streptomycin (11.6%), ciprofloxacin (9.9%), and kanamycin (8.3%). Tetracycline resistance in E. faecalis was coded by tet(M) (65.8%), tet(O) (1.7%), and tet(W) (0.8%). The majority (78.3%) of the erythromycin resistant E. faecalis carried erm(B). The conjugative transposons Tn916 and Tn916/1545 family were detected in 30.2% and 34.6% of identified isolates, respectively. E. faecalis carried virulence genes including, gelatinase (gelE, 70.7%), aggregation substance (asa1, 33.2%), enterococcus surface protein (esp, 8.8%), and cytolysin (cylA, 8.8%). Phenotypic assays showed that 91.4% of isolates with gelE were gelatinolytic and 46.7% of isolates with asa1 aggregated. All isolates with cylA were hemolytic on human blood.

Impacts
This study shows that house flies in food handling/serving facilities carry antibiotic resistant and potentially virulent enterococci with a capacity for horizontal transfer of antibiotic resistance genes to other bacteria.

Publications

  • Macovei L. and L. Zurek. (2006) Ecology of antibiotic resistance genes: Characterization of enterococci from houseflies collected in food settings. Applied and Environmental Microbiology 72: 4028-4035.
  • Sanderson MW, Sargeant JM, Shi X, Nagaraja TG, Zurek L, Alam MJ. (2006). Longitudinal emergence and distribution of Escherichia coli O157 genetic strains in a beef feedlot. Applied and Environmental Microbiology 72: 7614-7619.


Progress 09/01/05 to 08/31/06

Outputs
The project started 9/1/05. One postdoctoral research associate and one graduate student (MS) have been hired. The first sampling of the bison manure has been conducted on Nov. 11 resulting in 101 enterococcal isolates. These are currently processed for identification and antibiotic resistance and virulence by phenotype and genotype.

Impacts
The ecology of antibiotic resistance and virulence genes in the environment is not well understood. In this study, we will assess the role of insects in dissemination antibiotic resistant enterococci in the rural and urban environment.

Publications

  • No publications reported this period