United States Environmental Protection Agency Water Engineering Research Laboratory Cincinnati OH 45268 Research and Development EPA/600/S2-87/010 Apr. 1987 Project Summary Evaluation of Bacteroides as Indicator Bacteria in Drinking Water James T. Staley, Thomas T. Moench, N. Robert Ward, and Donald L. Johnstons Research was undertaken to examine the feasibility of using the Bacteroides fragilis group of intestinal bacteria as indicators of fecal contamination in drinking water. This group surpasses Escherichia coli in fulfilling criteria for an ideal microbial indicator of fecal con- tamination. Two immunological approaches— fluorescent antibody (FA) and enzyme- linked immunosorbent assay (ELISA)— were used to detect and quantify intestinal Bacteroides spp. in the labo- ratory and in simulated contaminated drinking water supplies that were seeded with fecal material from raw sewage. FA procedures did detect intestinal Bacteroides spp. in sewage-contami- nated waters, but full quantitative re- covery was not attained. Although an extensive effort was made to develop an ELISA test, considerable difficulty was encountered in the nonspecific ad- sorption of goat anti-rabbit peroxidase to filters. Thus this approach is not ad- visable until this problem can be over- come. Viable counting of intestinal Bac- teroides spp. from simulated raw- sewage-contaminated drinking waters indicates that there is a need for better selective and differential med" for this purpose. This Project Summary was devel- oped by EPA's Water Engineering Research Laboratory, Cincinnati. OH. to announce key findings of the research project that is fully docu- mented in a separate report of the same title (see Project Report ordering information at back). Introduction The ability to determine the quality of drinking water is essential to protecting the public health. In particular, it is nec- essary to know whether drinking water contains fecal material from humans or animals, since its presence indicates the possibility of intestinal pathogens in the water. Because pathogens would be ex- pected to occur in low numbers relative to the total bacteria from feces, tests have been designed to detect Es- cherichia coli, a normally nonpatho- genic bacterium that is indigenous to the intestinal tract of humans and other animals. Unfortunately, no simple and rapid test exists to determine whether E. coli is present in a water sample. In- stead, lengthy cultivation tests (requir- ing at least 24 to 48 hr of incubation) must be used to determine the presence of total and fecal coliform species, which are only presumptive indicators of the presence of E. coli. The ideal microbial indicator of fecal contamination should have the follow- ing features: (a) it should occur in large numbers in the intestinal tract of humans, (b) it should grow only in the intestinal tract and not in the habitat, and (c) it should be sufficiently distinc- tive so that it can be identified quickly with simple tests that are inexpensive. This research project examined the feasibility of using the Bacteroides frag- ilis group of intestinal bacteria as indica- tors of fecal contamination because this ------- group surpasses E. coli in fulfilling the three criteria outlined above. First, members of the enteric Bacteroides group (B. fragilis, B. vulgatus, B. ovatus, B. thetaiotaomicron, and B. distasonis) occur in much higher numbers (100 to 1000-fold greater concentrations) in the normal human intestinal tract than E. coli. Second, because the B. fragilis group comprises obligate rather that facultative anaerobes, they cannot grow in aerobic receiving waters. Finally, un- like E. coli, there are specific immuno- logical tests for this group that could potentially be used to quantitate them rapidly in water samples. This project examined the use of two immunological approaches—fluores- cent antibody (FA) and enzyme-linked immunosorbent assay (ELISA) proce- dures—to detect and quantify intestinal Bacteroides spp. in the laboratory and in simulated contaminated drinking water supplies that were seeded with fecal material from raw sewage. Materials and Methods Pure cultures of Bacteroides spp., pri- marily B. fragilis and B. vulgatus, were grown anaerobically m either Gas Pak containers* (BBL Laboratories) or in an anaerobic glove bag (Coy Laboratories, Ann Arbor, Michigan). Several media were used for pure culture work and also for viable enumeration of environ- mental Bacteroides spp., including brain heart infusion (BHI), which is a nonselective medium, as well as a vari- ety of selective and differential media, including the medium of Wilkins and Chalgren (WC), Bacteroides bile esculin (BBE), and kanamycin bile (KB). Faculta- tive anaerobes were grown aerobically on R2A medium. Antisera against Bacteroides spp. were tested. These included a polyva- lent commercial preparation, Fluorotec- F (General Diagnostics, Morris Plains, New Jersey), as well as specific rabbit preparations against B. fragilis and 6. vulgatus. The Fluorotec-F serum was used for direct fluorescent microscopic counting (dFA), whereas antisera for 6. fragilis and B. vulgatus were labeled with goat anti-rabbit serum conjugated to fluorescein (Miles-Yeda Ltd., Israel) for indirect fluorescent microscopic counting (iFA). These latter two sera were used for the ELISA testing in which 'Mention of trade names or commercial products does not constitute endorsement or recommenda- tion for use. goat anti-rabbit peroxidase (Miles- Yeda) was used as the enzyme. FA microscopic counting was per- formed on 0.2-u.m pore size Nuclepore filters that were prestained with irgalen black to reduce background fluores- cence. After filtration of the sample, 1.0 ml of a 2% hydrolyzed gelatin solution was added before exposure of the finer to Fluorotec-F (dFA) or anti-Bacteroides serum (iFA). Following appropriate in- cubation, washing, and mounting pro- cedures, dFA counts were made using an epifluorescence microscope. For iFA counting, an additional incubation with fluorescent goat anti-rabbit serum was included. ELISA tests were performed using a variety of filters and pore sizes, includ- ing polysulfone (0.45 u,m), polypropy- lene (10 |xm), polycarbonate (0.2 n,m), polyvinylidine-fluoride (0.45 u,m), cellu- lose acetate (0.45 u.m), cellulose nitrate (0.45 u.m), and teflon (0.45 urn). To pre- vent the nonspecific binding of goat anti-rabbit peroxidase (GARP) to filters, a variety of proteins (including bovine serum albumin, gelatin, and goat nor- mal serum) were tested under a variety of conditions before exposure to GARP. To simulate the contamination of a drinking water supply, some experi- ments were performed, including the addition of one part of raw untreated wastewater to nine parts of lake water samples. In some experiments, pure cultures of B. vulgatus and/or B. fragilis were seeded in addition. Samples were withdrawn at periodic intervals and enumerated by iFA and viable plating procedures. Oxygen concentrations were measured, .and all flasks were found to be aerobic (near oxygen satu- ration) shortly after initiation of the ex- periment and 24 hr later. Experimental Results Fluorescence Microscope Counting of Intestinal Bacteroides spp. Pure culture studies of 6. vulgatus showed that the iFA counts remained high throughout the ^rowth curve, par- alleling culture turbidity even after vi- ability declined appreciably (Table 1). This result indicates that the iFA proce- dure closely follows the optical density and total microscopic count in cultures of this numerically important intestinal Bacteroides spp. Recovery experiments were per- formed in which B. fragilis was added to buffered water, tap water, or primary wastewater and recovered by viable plating and dFA counting. Although high recoveries (36% to 96% of the vi- able count) were obtained from buf- fered water suspensions, lower recover- ies were obtained from tap water (8% to 32%) and primary wastewater (5% to 11%). The low recoveries from waste- waters were partly due to the large amount of detritus that interfered with the fluorescence microscope counting. In another experiment, a pure culture of 6. vulgatus was inoculated into filter- sterilized lake water and incubated aer- obically at 17°C. Cell counts by iFA indi- cated there was no decline in numbers following 3 days of incubation. These experiments demonstrate that fluorescent antibody counts of Bac- teroides spp. can be made with pure cultures in media and when inoculated into natural environmental samples of lake water, tap water, and wastewater. ELISA Test for Bacteroides spp. The ELISA methodology was thought to be a more effective means of assess- ing intestinal Bacteroides spp. in natural samples than fluorescent antibody pro- cedures for several reasons. First, the microscopic procedure is tedious and requires considerable time to perform. Also, it was thought that the problem of detrital interference might be partly cir- cumvented by the use of the ELISA pro- cedure. Because drinking water samples that would be tested for Bacteroides would have to be concentrated before exami- nation, efforts of this study were di- rected toward the development of an ELISA procedure that would use a mem- brane filtration step. However, prob- lems were encountered in preventing the goat anti-rabbit peroxidase from nonspecifically binding to filters. De- spite the use of various types of pore sizes of filters and several pretreatment procedures, this problem could not be resolved. Fluorescent Antibody Enumeration of B. fragilis and B. vulgatus in Simulated Contaminated Drinking Waters Because of the difficulties encoun- tered in the development of an ELISA test, efforts were directed toward exam- ining fluorescent antibody and viable counting procedures for recovering Bacteroides spp. from drinking waters. Since there was no assured source of ------- drinking water that was contaminated by Bacteroides spp., a simulated one was used. Raw wastewater was added to lake water and incubated aerobically. In some experiments, a pure culture of B. vulgatus (the most common human intestinal species) or a combination of 6. vulgatus and B. fragilis was seeded into the contaminated water. Bac- teroides spp. were enumerated on sev- eral selective and differential media and also by use of iFA techniques. The data in Figure 1 show the results of one of the experiments using artifi- cially contaminated water. In this exper- iment, pure cultures of Bacteroides were not seeded, so the counts that are shown are representative of what would be found in a natural situation. First note that the iFA counts were the highest of all, remaining in excess of 105/mL at zero time on days 1 and 2, and declining only slightly below that level on day 3. This result indicates that the FA technique can detect Bacteroides spp. (a pooled antiserum of B. vulgatus and B. fragilis was used) in a simulated contamination of drinking water. Viable counts of presumptive Bac- teroides spp. on WC medium were higher than total coliforms at zero time, whereas other media gave results com- parable with those found for total and fecal coliform bacteria (Figure 1). How- ever, when cultures of the presumptive Bacteroides were isolated and charac- terized, it was discovered that most could not be Bacteroides because they were facultative anaerobes rather than obligate anaerobes. Thus the actual lev- els of viable Bacteroides spp. in this ex- periment (as well as another that was performed) indicated that this group died off much more quickly than would have been predicted from pure culture studies. Thus no adequate selective and dif- ferential procedure presently exists for viable counting of Bacteroides spp. for water samples contaminated with raw sewage. Conclusions The results of this study indicate that FA procedures can detect intestinal Bac- teroides spp. in waters that have been contaminated with raw sewage. How- ever, full quantitative recovery was not attained by this procedure for two rea- sons: a) problems occurred with detrital interference, which obscured fluoresc- ing cells and gave rise to background fluorescence, and b) several serotypes Table 1. Comparison of Various Enumeration Procedures during Growth ofB. vulgatus Number of Cells/mL (x W7) Hours After Inoculation 7.5 11.5 25 36 218 Optical Density (660 nm) 0.08 0.21 0.46 0.46 0.49 Direct Micro- scopic Count 5.6 29 63 N.D.* 58 (Fa Count 6.1 27 42 64 45 Viable Count 3.7 22 35 54 0.07 *Not determined. Ol o D Figure 1. Time (days) Comparison of various techniques for enumeration of bacteria from a simulated contaminated drinking water source at daily intervals following contamination FA is the indirect fluorescent antibody count using pooled B vulgatus and B fragilis sera. Total coliform and fecal coliform bacteria were enumerated by standard methods, and three media (BBE. WC, and KB agar) were used for plating of viable Bacteroides spp. (see text for details). ------- existed among the intestinal Bac- teroides spp., and a better polyvalent antiserum (comparable to or better than the Fluorotec-F, which is no longer com- mercially available) would be needed to obtain better recovery. Furthermore, microscopic counting procedures are tedious and laborious and therefore not as desirable as other procedures such as ELISA testing. Although an extensive effort was made to develop an ELISA test, consid- erable difficulty was encountered in the nonspecific adsorption of goat anti- rabbit peroxidase to filters. Until this problem can be overcome, it is inadvis- able to consider using this approach. Viable counting of intestinal Bac- teroides spp. from simulated raw- sewage-contaminated drinking waters indicates that there is a need for better selective and differential media for this purpose. However, even if a better medium were to be developed, its use- fulness is questionable for two reasons: a) it would be no more rapid than cur- rent methods already developed for the enumeration of coliform bacteria, and b) Bacteroides spp. appear to die off quickly in raw sewage (i.e., much more quickly than Escherichia coli). One pos- sible advantage of such a test would be to assess how recently a water supply had been contaminated by raw sewage. Thus if a high ratio of Bacteroides spp. to fecal coliforms was found, it would suggest recent contamination, whereas a low ratio would suggest earlier con- tamination. The full report was submitted in fulfill- ment of Cooperative No. CR-810477-01- 3 by the University of Washington under the sponsorship of the U.S. Envi- ronmental Protection Agency. James T. Staley, Thomas T. Moench, and N. Robert Ward are with University of Washington, Seattle, WA 98195; and Donald L Johnstone is with Washington State University, Pullman, WA 99164. Donald Reasoner is the EPA Project Officer (see belowj. The complete report, entitled "Evaluation of Bacteroides as Indicator Bacteria in Drinking Water," (Order No. PB 87-145 892/AS; Cost: $11.95, subject to change) will be available only from: National Technical Information Service 5285 Port Royal Road Springfield, VA 22161 Telephone: 703-487-4650 The EPA Project Officer can be contacted at: Water Engineering Research Laboratory U.S. Environmental Protection Agency Cincinnati, OH 45268 United States Environmental Protection Agency Center for Environmental Research Information Cincinnati OH 45268 BULK RATE POSTAGE & FEES PAI EPA PERMIT No G-35 Official Business Penalty for Private Use S300 EPA/600/S2-87/010 0169064 tfERL RfcbXUN V CHICAGO XL 60604 ------- |