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Microbial antagonism: A potent defense against infection
Clinical Microbiology Newsletter Vol. 4, No. 18
September 15, 1982
Microbial Antagonism: A Potent Defense Against Infection W. Eugene Sanders, Jr., M.D. Professor and Chairman and
Christine C. Sanders, Ph.D. Associate Professor Department of Medical Microbiology Creighton University School of Medicine Omaha, Nebraska 68178
Science is once again discovering the wisdom of the founders of medical microbiology. In 1877, Pasteur and Joubert observed inhibition of growth of the anthrax bacillus in urine contaminated by "common" microorganisms and speculated that these contaminants might be useful in the prevention or treatment of anthrax. In 1909, Schiotz noted that a patient with staphylococcal disease did not develop diphtheria after having been admitted inadvertently to a diphtheria ward. Schiotz then deliberately sprayed suspensions of staphylococci into the throats of diphtheria carriers and claimed "good results." Early in this century Metchnikoff became the champion of the use of harmless saprophytes, such as lactobacilli, to prevent or treat a variety of bacterial diseases (3, 7). However, the antibiotic era supervened, and interest in interbacterial antagonisms waned. More recently, the many failures of antibiotic prophylaxis and the adverse consequences of the suppression of normal bacterial flora have evoked renewed interest. Thus, more than a century after Pasteur's original speculation, many
are attempting to define and exploit naturally occurring microbial antagonisms. The normal bacterial flora of healthy humans is acquired at a very early age, often within hours of birth. The flora rapidly becomes a remarkably stable ecosystem. There is a balance of dynamic interactions, rather than indifference, among its constituents. Additive or synergistic interactions appear to be in equilibrium with those that are antagonistic. This complex ecosystem is also in dynamic equilibrium with the host. New species of harmless organisms and most exogenously acquired pathogens may enter this microcosm only after introduction of very large inocula or suppression of the flora or the host's other natural defenses (3, 7). The normal flora has been convincingly implicated in host resistance to a broad range of infectious diseases and intoxications. However, the specific components of the flora that contribute to this resistance have been less well characterized, and in only a few instances have the mechanisms of antagonism been elucidated. We will review briefly several of the clinical situations that have been studied in depth.
staphylococcus, strain S02A, were resistant to colonization by an epidemic strain of Staphylococcus aureus, phage type 80/81 (9). Subsequently, strain S02A was deliberately implanted into the anterior nares and onto the umbilical stumps of newborn infants. It was shown that the organism persisted and conferred resistance to colonization by more virulent strains of S. aureus. Artificial implantation of S02A was then used successfully to control epidemics of staphylococcal disease in newborn nurseries. Subsequently, implantation of S02A into the nares and onto the skin resulted in clinical improvement in approximately 80070 of patients with staphylococcal furunculosis (1). The discovery of potent antistaphylococcal drugs and the occurrence of occasional pustular skin lesions due to S02A have limited the use of this organism. However, the experience with 502A proved unequivocally
In This Issue Microbial Antagonism 127 Clinical importance and mechanisms of antagonistic microbial interactions National Scientific Meetings ....• 130 Are they still worthwhile?
Clinical Importance of Microbial Antagonism
Shigella Bacteremia Report 0/ this unusual aspect of infection
In 1959, Shinefield et al. recognized that infants naturally colonized by a relatively avirulent
Letters . . . . . . . • • • . . . . . . . . . . . . . 131 Workshops and Meetings
131
132
that manipulation of the flora was effective in the prophylaxis of colonization and disease. Sprunt et al. have demonstrated an association between naturally occurring inhibitory pharyngeal flora and resistance to colonization of the throat with gram-negative bacilli (11). The most active inhibitors were a-hemolytic streptococci. In controlled studies, the selection of penicillin-resistant inhibitors by oral administration of low doses of the drug has been shown to prevent colonization by gram-negative bacilli during subsequent parenteral therapy with high doses of penicillin. More recently, the deliberate implantation of an inhibitory a-hemolytic streptococcus has resulted in the elimination of gramnegative bacilli from the pharyngeal flora of neonates in an intensive care unit (10). We have studied the effect of pharyngeal flora upon the susceptibility of children to group A streptococcal infection (2). In a prospective study, an inverse correlation was noted between inhibitory activity of the throat flora and the rate of acquisition of epidemic group A streptococci. The presence of
organisms that were bactericidal in vitro for group A streptococci was most closely associated with resistance. Most bactericidal inhibitors were non-hemolytic streptococci. Children who became infected were devoid of inhibitory flora or harbored bacteriostatic organisms, predominantly a-hemolytic streptococci. Saigh, Sanders, and Sanders have studied interactions between the endocervical flora and Neisseria gonorrhoeae in women (6). Streptococci, staphylococci, and lactobacilli were potent inhibitors of gonococcal growth in vitro. However, only inhibitory lactobacilli were associated with resistance to gonorrhea. Among women having contact with an infected partner, those who subsequently developed gonorrhea were significantly less likely to have inhibitory lactobacilli than those who did not become infected following the exposure. Since lactobacilli were shown to be most prevalent during the two weeks following menses, this may also account for the lower incidence of gonorrhea in the intermenstrual period. In the same population, an inverse correlation was
demonstrated between the presence of lactobacilli and strains of S. aureus in the endocervix of young women. Lactobacilli were most prevalent in the intermenstrual period, while S. aureus was most often recovered during menses. The inhibition of staphylococci by the lactobacilli was then shown to be dependent upon the availability of a variety of substrates. It was thus hypothesized that the toxic-shock syndrome may result in part from the depletion of essential substrates by superabsorbent tampons and the resultant reduction in inhibitory activity of the lactobacilli (8). In a frequently overlooked but highly significant study, Roberts identified the role of indigenous flora in resistance to wound infections (4). The wounds of 390 patients undergoing clean orthopedic surgery were cultured extensively prior to closure. No antibiotics were given prophylactically or for treatment of subsequent wound infections until appropriate cultures were obtained. The overall wound infection rate was 6%. In patients who harbored a potentially pathogenic organism (S. aureus, enteric bacilli, etc.) in the wound at
Table 1 Mechanisms of Microbial Antagonisms and Examples of Their Possible Role in Host Defense Mechanism
Site
Inhibitor (Effector)
Target Organism
Pharynx
a-hemolytic streptococci
Group A streptococci
Colon
Escherichia coli
Enteric organisms, Shigella
Skin, nares
Staphylococcus sp.
S. aureus
Colon Colon
Escherichia coli Bacteroides sp,
Shigella Salmonella, Shigella
Respiratory tract
a- and non-hemolytic
Group A streptococci, enteric bacilli
streptococci Non-hemolytic streptococci e-hemolytic streptococci
Group A streptococci Group A streptococci, enteric bacilli
Staphylococcus sp.
S. aureus
Competition for essential substrates
Purines, pyrimidines, vitamins. amino acids
Carbon sources (dulcitol, sucrose, etc.)
Nicotinamide Creation of a restrictive physiologic environment
Reduced redox potential Acids: volatile fatty acids, acetic, others Elaboration of antibacterial substances
Hydrogen peroxide and acid Enocin (inhibits pantothenate utilization) Viridins (bacteriocin-like) Competition for
128
tissu~1f:JJ;S..
Pharynx Respiratory tract
Clinical Microbiology Ncwslcttcr
the time of closure, the subsequent rate of infection was 24%; and in every patient but one, the wound infection was due to the same organism that had been isolated earlier from the operative site. In patients whose surgical site was bacteriologically sterile, only 5% developed a wound infection. However, in patients whose operative site was contaminated with normal flora (diphtheroids, micrococci, oral streptococci, etc.) the subsequent rate of infection was only 1 %. Thus from the patient's standpoint, it was more advantageous to have had wound contamination with commensals rather than a sterile operative site at the time of closure. In addition, these results provide a possible explanation for those studies in which the wound infection rate increased after administration of prophylactic antibiotics to patients undergoing clean or minor surgery. It is quite possible that the antimicrobials were more effective in suppressing the protective flora rather than any potential pathogen. The role of indigenous flora in resistance to infection of the gastrointestinal tract has been recognized for years. However, because of the complexity of the flora it has been difficult to identify specific organisms that contribute to resistance. In experimentally infected animals, it appears that the resistance to salmonellosis and shigellosis conferred by the micro flora is multifactorial. Escherichia coli and Bacteroides species have been most often implicated, and they may inhibit target pathogens by a variety of mechanisms (Table 1). Antibiotic-induced pseudomembranous enterocolitis undoubtedly results from the inhibition of gastrointestinal flora that normally suppresses growth or toxin production, or both, by indigenous or newly acquired strains of Clostridium difficile.
Mechanisms of Microbial Antagonisms Microorganisms may interact antagonistically by anyone or a
Copyright
1982 by G. K. Hall & Co.
combination of four possible mechanisms (Table 1). The inhibitor may compete more effectively for substrates essential for the growth and survival of the target organism. The inhibitor may create a physiologic environment that is inimical to the replication of other microorganisms. Antagonism may also result from the elaboration of antibiotic substances or from competition between microorganisms for a limited number of tissue receptors or other similar ecologic niches. The interactions between some bacteria may be extremely complex. For example, pharyngeal streptococci appear to antagonize group A streptocci by three of the four possible mechanisms, and some strains may elaborate at least three distinct antibiotic substances. Inhibition of growth of a group A streptococcus by a highly active non-hemolytic streptococcal strain is shown in Figure 1. Despite the extensive studies performed to date, the mechanisms by which most organisms (including pharyngeal streptococci) act are still undefined and clearly differ from those listed in the table.
The Future The ultimate goal of the study of microbial interactions is the exploitation of naturally occurring microbial antagonisms to prevent or treat infectious diseases. It is increasingly clear that some individuals become endowed, often shortly after birth, with a flora that is highly inhibitory, or even lethal, for a variety of exogenously acquired pathogens. Others lack this beneficial flora. Perhaps, in the future, the acquisition of normal flora need not be left to chance encounters with close contacts and the environment. It should be possible to implant a highly inhibitory flora and ensure that it is maintained throughout illness and antimicrobial therapy. Many opportunities to follow up on the predictions of our scientific predecessors await clinicians and microbiologists at the bedside and at the bench. It should be
Fig. 1. Antagonism of growth of a group A streptococcus by a nonhemolytic pharyngeal streptococcus. Varying dilutions of an overnight culture of the inhibitory strain have been spotted onto a lawn of group A streptococci.
remembered that whenever two or more microorganisms encounter each other in the patient or in culture, the interaction will almost certainly not be one of indifference. References
1. Boris, M., et al, 1968. Bacterial interference. Protection against recurrent intrafamilial staphylococcal disease. Am. J. Dis. Child. 115:521-529. 2. Crowe (Sanders), C.
c.,
W. E.
Sanders, Jr., and S. Longley. 1973. Bacterial interference. II. Role of the normal throat flora in prevention of colonization bf group A streptococcus. J. Infect. Dis. 128:527-532.
3. Florey, H. W. 1946. The use of microorganisms for therapeutic purposes. Yale J. BioI. Med. 19: 101-118. 4. Roberts, D. R. 1965. Significance of clean wound cultures. Am. Surg. 31:153-155. 5. Rolfe, R. D., S. Helebian, and S.
M. Finegold. 1981. Bacterial interference between Clostridium difficile and normal fecal flora. J. Infect. Dis. 143:470-475. 6. Saigh, J. H., C. C. Sanders, and W. E. Sanders, Jr. 1978. Inhibition of Neisseria gonot rhoeae by aerobic and facultatively anaerobic components of the endocervical flora: Evidence for a protective effect against infection. Infect. Immun. 19:704-710. 7. Sanders, W. E., Jr. 1975. Interac-
tions between streptococci and other bacteria in the throat, pp. 106-109. In D. Schlessinger (ed.), Micro-
129
biology-197S. American Society for Microbiology, Washington, D.C. 8. Sanders, C. C., W. E. Sanders, Jr., and J. E. Fagnant. 1982. Toxic shock syndrome: An ecologic imbalance within the genital microflora of women. Am. J. Obstet, Gynecol. 142:977-982. 9. Shinefield, H. R., J. C. Ribble, and
M. Boris. 1971. Bacterial interference between strains of Staphylococcus aureus. Am. J. Dis. Child. 121:148-1S2. 10. Spront, K., G. Leidy, and W. Redman. 1980. Abnormal colonization of neonates in an ICU: Conversion to normal colonization by pharyngeal implantation of alpha
hemolytic streptococcus strain 215. Pediatr. Res. 14:308-313. 11. Sprunt, K., and W. Redman. 1968. Evidence suggesting importance of role of interbacterial inhibition in maintaining balance of normal flora. Ann. Intern. Med. 68:579-590.
microbiologists. The 1982 national ASM program was composed of 2,024 papers, 72 seminars, 5 round tables, 5 symposia, 3 councillors' colloquia, and several special lectures. Most of these were scientific sessions, but for several years some have been devoted to subjects such as the patenting of life forms, the status of women and minorities in microbiology, cooperation between industry and universities, health care legislation and clinical microbiology, infection control in hospitals, and environmental hazards (pathogens and chemicals). In addition to the annual meeting, the ASM, with the Infectious Diseases Society of America, sponsors an Interscience Conference on Antimicrobial Agents and Chemotherapy, which brings together scientists and physicians for in-depth discussions of infectious diseases. Large meetings provide many advantages, but some people perceive them as impersonal; "large" does not necessarily imply impersonal or unresponsive, nor should it suggest the dilution of subject matter within a field. A national meeting provides an opportunity to bring together authorities for the presentation of new data and debate on their interpretation. Small meetings also are arranged within the framework of the large one. At the ASM national meeting, professional enlightenment and improved professional status are afforded through symposia and seminars sponsored by the Board on Public and Scientific Affairs involving national issues such as federal budgets for health care and
recombinant DNA. Criteria and standards are developed for the profession by the National Registry of Microbiologists, the American Board of Medical Microbiology, the American Board of Medical Laboratory Immunology, and the American Academy of Microbiology. The Board of Education and Training initiates and administers a variety of programs designed to improve professional competence in microbiology. These programs include workshops, innovations in undergraduate, graduate, and continuing education, and educational materials. Category 1 continuing education credits are available at the national meeting. The Placement Service at the national ASM annual meetings brings together prospective employers and employees. Microbiologists at all levels who desire position changes are interviewed by prospective employers during the meeting. This year, 195 positions were offered to 218 registrants. At the 1982 ASM annual meeting attendees were able to see the latest diagnostics, laboratory products, supplies, instruments, books, and services at more than 500 commercial exhibits. Exhibitors were able to learn the needs of attendees and to provide useful information. Exhibits of this size and quality are expensive. Exhibiting companies are attracted to the ASM annual meetings by the number and caliber of members attending and the diversity of specialties represented. Smaller meetings or those limited to narrow fields of interest are less attractive to many exhibitors.
Editorial What do National Scientific Meetings Offer? Riley D. Housewright, Ph.D. Executive Director American Society for Microbiology Washington, D.C. 20006
The increased cost of attending national meetings and a decrease in the funds available for such purposes have caused some reflection on the need for such meetings. The major purpose of any scientific meeting is the exchange of knowledge with one's colleagues. This purpose can be achieved to some degree at local, regional, national, or international meetings. Knowledge, however, is not a geographic commodity. Regions vary in interests, enlightenment, and exposure to university, industrial, government, hospital, or other laboratories. At national meetings, experts in many theoretical and applied fields develop information networks that would not be possible at smaller regional meetings. An excellent way to become scientifically provincial is to limit professional information exchange. A national meeting can provide an important counterbalance to such provincialism. This year, the national annual meeting of the American Society for Microbiology (ASM) attracted approximately 10,500 scientists from 41 nations for 5 days. Nineteen disciplinary divisions were represented on the program. The largest division was Clinical Microbiology, but the programs of several other divisions also contributed information valuable to clinical
130
Clinical Microbiology Newsletter
September 15, 1982
Microbial Antagonism: A Potent Defense Against Infection W. Eugene Sanders, Jr., M.D. Professor and Chairman and
Christine C. Sanders, Ph.D. Associate Professor Department of Medical Microbiology Creighton University School of Medicine Omaha, Nebraska 68178
Science is once again discovering the wisdom of the founders of medical microbiology. In 1877, Pasteur and Joubert observed inhibition of growth of the anthrax bacillus in urine contaminated by "common" microorganisms and speculated that these contaminants might be useful in the prevention or treatment of anthrax. In 1909, Schiotz noted that a patient with staphylococcal disease did not develop diphtheria after having been admitted inadvertently to a diphtheria ward. Schiotz then deliberately sprayed suspensions of staphylococci into the throats of diphtheria carriers and claimed "good results." Early in this century Metchnikoff became the champion of the use of harmless saprophytes, such as lactobacilli, to prevent or treat a variety of bacterial diseases (3, 7). However, the antibiotic era supervened, and interest in interbacterial antagonisms waned. More recently, the many failures of antibiotic prophylaxis and the adverse consequences of the suppression of normal bacterial flora have evoked renewed interest. Thus, more than a century after Pasteur's original speculation, many
are attempting to define and exploit naturally occurring microbial antagonisms. The normal bacterial flora of healthy humans is acquired at a very early age, often within hours of birth. The flora rapidly becomes a remarkably stable ecosystem. There is a balance of dynamic interactions, rather than indifference, among its constituents. Additive or synergistic interactions appear to be in equilibrium with those that are antagonistic. This complex ecosystem is also in dynamic equilibrium with the host. New species of harmless organisms and most exogenously acquired pathogens may enter this microcosm only after introduction of very large inocula or suppression of the flora or the host's other natural defenses (3, 7). The normal flora has been convincingly implicated in host resistance to a broad range of infectious diseases and intoxications. However, the specific components of the flora that contribute to this resistance have been less well characterized, and in only a few instances have the mechanisms of antagonism been elucidated. We will review briefly several of the clinical situations that have been studied in depth.
staphylococcus, strain S02A, were resistant to colonization by an epidemic strain of Staphylococcus aureus, phage type 80/81 (9). Subsequently, strain S02A was deliberately implanted into the anterior nares and onto the umbilical stumps of newborn infants. It was shown that the organism persisted and conferred resistance to colonization by more virulent strains of S. aureus. Artificial implantation of S02A was then used successfully to control epidemics of staphylococcal disease in newborn nurseries. Subsequently, implantation of S02A into the nares and onto the skin resulted in clinical improvement in approximately 80070 of patients with staphylococcal furunculosis (1). The discovery of potent antistaphylococcal drugs and the occurrence of occasional pustular skin lesions due to S02A have limited the use of this organism. However, the experience with 502A proved unequivocally
In This Issue Microbial Antagonism 127 Clinical importance and mechanisms of antagonistic microbial interactions National Scientific Meetings ....• 130 Are they still worthwhile?
Clinical Importance of Microbial Antagonism
Shigella Bacteremia Report 0/ this unusual aspect of infection
In 1959, Shinefield et al. recognized that infants naturally colonized by a relatively avirulent
Letters . . . . . . . • • • . . . . . . . . . . . . . 131 Workshops and Meetings
131
132
that manipulation of the flora was effective in the prophylaxis of colonization and disease. Sprunt et al. have demonstrated an association between naturally occurring inhibitory pharyngeal flora and resistance to colonization of the throat with gram-negative bacilli (11). The most active inhibitors were a-hemolytic streptococci. In controlled studies, the selection of penicillin-resistant inhibitors by oral administration of low doses of the drug has been shown to prevent colonization by gram-negative bacilli during subsequent parenteral therapy with high doses of penicillin. More recently, the deliberate implantation of an inhibitory a-hemolytic streptococcus has resulted in the elimination of gramnegative bacilli from the pharyngeal flora of neonates in an intensive care unit (10). We have studied the effect of pharyngeal flora upon the susceptibility of children to group A streptococcal infection (2). In a prospective study, an inverse correlation was noted between inhibitory activity of the throat flora and the rate of acquisition of epidemic group A streptococci. The presence of
organisms that were bactericidal in vitro for group A streptococci was most closely associated with resistance. Most bactericidal inhibitors were non-hemolytic streptococci. Children who became infected were devoid of inhibitory flora or harbored bacteriostatic organisms, predominantly a-hemolytic streptococci. Saigh, Sanders, and Sanders have studied interactions between the endocervical flora and Neisseria gonorrhoeae in women (6). Streptococci, staphylococci, and lactobacilli were potent inhibitors of gonococcal growth in vitro. However, only inhibitory lactobacilli were associated with resistance to gonorrhea. Among women having contact with an infected partner, those who subsequently developed gonorrhea were significantly less likely to have inhibitory lactobacilli than those who did not become infected following the exposure. Since lactobacilli were shown to be most prevalent during the two weeks following menses, this may also account for the lower incidence of gonorrhea in the intermenstrual period. In the same population, an inverse correlation was
demonstrated between the presence of lactobacilli and strains of S. aureus in the endocervix of young women. Lactobacilli were most prevalent in the intermenstrual period, while S. aureus was most often recovered during menses. The inhibition of staphylococci by the lactobacilli was then shown to be dependent upon the availability of a variety of substrates. It was thus hypothesized that the toxic-shock syndrome may result in part from the depletion of essential substrates by superabsorbent tampons and the resultant reduction in inhibitory activity of the lactobacilli (8). In a frequently overlooked but highly significant study, Roberts identified the role of indigenous flora in resistance to wound infections (4). The wounds of 390 patients undergoing clean orthopedic surgery were cultured extensively prior to closure. No antibiotics were given prophylactically or for treatment of subsequent wound infections until appropriate cultures were obtained. The overall wound infection rate was 6%. In patients who harbored a potentially pathogenic organism (S. aureus, enteric bacilli, etc.) in the wound at
Table 1 Mechanisms of Microbial Antagonisms and Examples of Their Possible Role in Host Defense Mechanism
Site
Inhibitor (Effector)
Target Organism
Pharynx
a-hemolytic streptococci
Group A streptococci
Colon
Escherichia coli
Enteric organisms, Shigella
Skin, nares
Staphylococcus sp.
S. aureus
Colon Colon
Escherichia coli Bacteroides sp,
Shigella Salmonella, Shigella
Respiratory tract
a- and non-hemolytic
Group A streptococci, enteric bacilli
streptococci Non-hemolytic streptococci e-hemolytic streptococci
Group A streptococci Group A streptococci, enteric bacilli
Staphylococcus sp.
S. aureus
Competition for essential substrates
Purines, pyrimidines, vitamins. amino acids
Carbon sources (dulcitol, sucrose, etc.)
Nicotinamide Creation of a restrictive physiologic environment
Reduced redox potential Acids: volatile fatty acids, acetic, others Elaboration of antibacterial substances
Hydrogen peroxide and acid Enocin (inhibits pantothenate utilization) Viridins (bacteriocin-like) Competition for
128
tissu~1f:JJ;S..
Pharynx Respiratory tract
Clinical Microbiology Ncwslcttcr
the time of closure, the subsequent rate of infection was 24%; and in every patient but one, the wound infection was due to the same organism that had been isolated earlier from the operative site. In patients whose surgical site was bacteriologically sterile, only 5% developed a wound infection. However, in patients whose operative site was contaminated with normal flora (diphtheroids, micrococci, oral streptococci, etc.) the subsequent rate of infection was only 1 %. Thus from the patient's standpoint, it was more advantageous to have had wound contamination with commensals rather than a sterile operative site at the time of closure. In addition, these results provide a possible explanation for those studies in which the wound infection rate increased after administration of prophylactic antibiotics to patients undergoing clean or minor surgery. It is quite possible that the antimicrobials were more effective in suppressing the protective flora rather than any potential pathogen. The role of indigenous flora in resistance to infection of the gastrointestinal tract has been recognized for years. However, because of the complexity of the flora it has been difficult to identify specific organisms that contribute to resistance. In experimentally infected animals, it appears that the resistance to salmonellosis and shigellosis conferred by the micro flora is multifactorial. Escherichia coli and Bacteroides species have been most often implicated, and they may inhibit target pathogens by a variety of mechanisms (Table 1). Antibiotic-induced pseudomembranous enterocolitis undoubtedly results from the inhibition of gastrointestinal flora that normally suppresses growth or toxin production, or both, by indigenous or newly acquired strains of Clostridium difficile.
Mechanisms of Microbial Antagonisms Microorganisms may interact antagonistically by anyone or a
Copyright
1982 by G. K. Hall & Co.
combination of four possible mechanisms (Table 1). The inhibitor may compete more effectively for substrates essential for the growth and survival of the target organism. The inhibitor may create a physiologic environment that is inimical to the replication of other microorganisms. Antagonism may also result from the elaboration of antibiotic substances or from competition between microorganisms for a limited number of tissue receptors or other similar ecologic niches. The interactions between some bacteria may be extremely complex. For example, pharyngeal streptococci appear to antagonize group A streptocci by three of the four possible mechanisms, and some strains may elaborate at least three distinct antibiotic substances. Inhibition of growth of a group A streptococcus by a highly active non-hemolytic streptococcal strain is shown in Figure 1. Despite the extensive studies performed to date, the mechanisms by which most organisms (including pharyngeal streptococci) act are still undefined and clearly differ from those listed in the table.
The Future The ultimate goal of the study of microbial interactions is the exploitation of naturally occurring microbial antagonisms to prevent or treat infectious diseases. It is increasingly clear that some individuals become endowed, often shortly after birth, with a flora that is highly inhibitory, or even lethal, for a variety of exogenously acquired pathogens. Others lack this beneficial flora. Perhaps, in the future, the acquisition of normal flora need not be left to chance encounters with close contacts and the environment. It should be possible to implant a highly inhibitory flora and ensure that it is maintained throughout illness and antimicrobial therapy. Many opportunities to follow up on the predictions of our scientific predecessors await clinicians and microbiologists at the bedside and at the bench. It should be
Fig. 1. Antagonism of growth of a group A streptococcus by a nonhemolytic pharyngeal streptococcus. Varying dilutions of an overnight culture of the inhibitory strain have been spotted onto a lawn of group A streptococci.
remembered that whenever two or more microorganisms encounter each other in the patient or in culture, the interaction will almost certainly not be one of indifference. References
1. Boris, M., et al, 1968. Bacterial interference. Protection against recurrent intrafamilial staphylococcal disease. Am. J. Dis. Child. 115:521-529. 2. Crowe (Sanders), C.
c.,
W. E.
Sanders, Jr., and S. Longley. 1973. Bacterial interference. II. Role of the normal throat flora in prevention of colonization bf group A streptococcus. J. Infect. Dis. 128:527-532.
3. Florey, H. W. 1946. The use of microorganisms for therapeutic purposes. Yale J. BioI. Med. 19: 101-118. 4. Roberts, D. R. 1965. Significance of clean wound cultures. Am. Surg. 31:153-155. 5. Rolfe, R. D., S. Helebian, and S.
M. Finegold. 1981. Bacterial interference between Clostridium difficile and normal fecal flora. J. Infect. Dis. 143:470-475. 6. Saigh, J. H., C. C. Sanders, and W. E. Sanders, Jr. 1978. Inhibition of Neisseria gonot rhoeae by aerobic and facultatively anaerobic components of the endocervical flora: Evidence for a protective effect against infection. Infect. Immun. 19:704-710. 7. Sanders, W. E., Jr. 1975. Interac-
tions between streptococci and other bacteria in the throat, pp. 106-109. In D. Schlessinger (ed.), Micro-
129
biology-197S. American Society for Microbiology, Washington, D.C. 8. Sanders, C. C., W. E. Sanders, Jr., and J. E. Fagnant. 1982. Toxic shock syndrome: An ecologic imbalance within the genital microflora of women. Am. J. Obstet, Gynecol. 142:977-982. 9. Shinefield, H. R., J. C. Ribble, and
M. Boris. 1971. Bacterial interference between strains of Staphylococcus aureus. Am. J. Dis. Child. 121:148-1S2. 10. Spront, K., G. Leidy, and W. Redman. 1980. Abnormal colonization of neonates in an ICU: Conversion to normal colonization by pharyngeal implantation of alpha
hemolytic streptococcus strain 215. Pediatr. Res. 14:308-313. 11. Sprunt, K., and W. Redman. 1968. Evidence suggesting importance of role of interbacterial inhibition in maintaining balance of normal flora. Ann. Intern. Med. 68:579-590.
microbiologists. The 1982 national ASM program was composed of 2,024 papers, 72 seminars, 5 round tables, 5 symposia, 3 councillors' colloquia, and several special lectures. Most of these were scientific sessions, but for several years some have been devoted to subjects such as the patenting of life forms, the status of women and minorities in microbiology, cooperation between industry and universities, health care legislation and clinical microbiology, infection control in hospitals, and environmental hazards (pathogens and chemicals). In addition to the annual meeting, the ASM, with the Infectious Diseases Society of America, sponsors an Interscience Conference on Antimicrobial Agents and Chemotherapy, which brings together scientists and physicians for in-depth discussions of infectious diseases. Large meetings provide many advantages, but some people perceive them as impersonal; "large" does not necessarily imply impersonal or unresponsive, nor should it suggest the dilution of subject matter within a field. A national meeting provides an opportunity to bring together authorities for the presentation of new data and debate on their interpretation. Small meetings also are arranged within the framework of the large one. At the ASM national meeting, professional enlightenment and improved professional status are afforded through symposia and seminars sponsored by the Board on Public and Scientific Affairs involving national issues such as federal budgets for health care and
recombinant DNA. Criteria and standards are developed for the profession by the National Registry of Microbiologists, the American Board of Medical Microbiology, the American Board of Medical Laboratory Immunology, and the American Academy of Microbiology. The Board of Education and Training initiates and administers a variety of programs designed to improve professional competence in microbiology. These programs include workshops, innovations in undergraduate, graduate, and continuing education, and educational materials. Category 1 continuing education credits are available at the national meeting. The Placement Service at the national ASM annual meetings brings together prospective employers and employees. Microbiologists at all levels who desire position changes are interviewed by prospective employers during the meeting. This year, 195 positions were offered to 218 registrants. At the 1982 ASM annual meeting attendees were able to see the latest diagnostics, laboratory products, supplies, instruments, books, and services at more than 500 commercial exhibits. Exhibitors were able to learn the needs of attendees and to provide useful information. Exhibits of this size and quality are expensive. Exhibiting companies are attracted to the ASM annual meetings by the number and caliber of members attending and the diversity of specialties represented. Smaller meetings or those limited to narrow fields of interest are less attractive to many exhibitors.
Editorial What do National Scientific Meetings Offer? Riley D. Housewright, Ph.D. Executive Director American Society for Microbiology Washington, D.C. 20006
The increased cost of attending national meetings and a decrease in the funds available for such purposes have caused some reflection on the need for such meetings. The major purpose of any scientific meeting is the exchange of knowledge with one's colleagues. This purpose can be achieved to some degree at local, regional, national, or international meetings. Knowledge, however, is not a geographic commodity. Regions vary in interests, enlightenment, and exposure to university, industrial, government, hospital, or other laboratories. At national meetings, experts in many theoretical and applied fields develop information networks that would not be possible at smaller regional meetings. An excellent way to become scientifically provincial is to limit professional information exchange. A national meeting can provide an important counterbalance to such provincialism. This year, the national annual meeting of the American Society for Microbiology (ASM) attracted approximately 10,500 scientists from 41 nations for 5 days. Nineteen disciplinary divisions were represented on the program. The largest division was Clinical Microbiology, but the programs of several other divisions also contributed information valuable to clinical
130
Clinical Microbiology Newsletter