The work of Professor John Tagg
Professor Tagg’s first significant encounter with Streptococcus pyogenes – the bacteria that causes strep sore throat – was as a 12-year old living in Melbourne. A series of sore throats culminated in him developing rheumatic fever. He then had to consume penicillin tablets daily over the following decade to help prevent any follow-up attacks of the disease. Fortunately, due to this antibiotic regime, he did not suffer any of the residual heart damage that can occur from recurrent episodes of rheumatic fever.
Following high school, John studied at Melbourne University, and in the third year of his Microbiology degree, he became influenced by the teachings of Dr Rose Mushin concerning the potential applications of bacterial interference as a targeted and natural means of infection prevention. Dr Mushin had become a devotee of an old-world strategy for infectious disease control, the origins of which pre-date the discovery of antibiotics and indeed can be traced back to the studies of Louis Pasteur.
Dr Mushin managed to convince the entire microbiology class to consume milk that had been seeded with so-called “friendly” Escherichia coli. These bacteria were equipped with a bacteriocin armament that would enable them, from their proposed site of lodgment in the intestinal tract, to kill any vulnerable salmonellae that happened to pass close by. Dr Mushin’s proposal sounded logical and feasible. Bacteriocins, she explained, were proteinaceous antibiotics produced by bacteria which had a bactericidal mode of action against various other relatively closely-related bacteria that were potentially capable of competing with them for occupancy of the same ecological niche (i.e. they were anti-competitor molecules).
As the young John Tagg listened to Dr Mushin it occurred to him that perhaps a similar strategy could be applied in the human oral cavity to gain some relatively-specific protection against S. pyogenes infections.
That insight provided him with an irresistible challenge – he now knew what he wanted to do.
His life’s work has been dedicated to finding good bacteria that could support oral health. His breakthrough came in the 1990s when he discovered that children who didn’t get many, or even any, sore throats had a rare balance of bacteria in their mouths. One strain of bacteria in particular was in abundance in their mouths and lacking in almost all the other mouths. That strain was named Streptococcus salivarius K12, or more commonly BLIS K12.
The birth of oral probiotics
The term probiotic (literally meaning ‘for life’) is a general term now widely used to refer to ‘live microorganisms which when administered in adequate amounts confer a health benefit on the host’. More specifically, ‘oral probiotics’ can be considered to be probiotics, the action and beneficial outcomes of which are a direct outcome of their interaction with microbial and/or host cellular components of the oral cavity. Thus, bona fide oral probiotics differ from the traditional orally-administered intestinal probiotics (i.e. yoghurts or other products comprising lactobacilli and bifidobacteria of intestinal origin). The latter do not primarily or persistently localize within the oral microbiota – even though some short-term beneficial outcomes may manifest within the oral cavity following their ingestion.
Every human harbors a personalised oral cavity microbiome, the presence of which is essential to heath maintenance, but also having a dark side capable of causing harm to host tissues, both oral and systemic. The biofilms coating every surface of the oral cavity comprise complex ecosystems that help to maintain our health when they are in equilibrium. Ecological shifts within the microbiome can sometimes allow pathogens that are either intrinsic to the biofilm (in a carriage state) or newly introduced to the oral cavity to become manifest and induce disease. The intentional seeding of the oral microbiome with harmless probiotics equipped with the capability of exerting targeted bacterial population control (i.e. bacterial interference or ‘germ warfare’) provides an approach to infection prevention that has as its basis the augmentation of naturally occurring processes. Within the oral cavity the principal bacterial infections that have to date been identified for probiotic intervention have been streptococcal pharyngitis, otitis media, halitosis and dental caries.
Successful implantation of the oral microbiota with BLIS K12 provides a potential means of preventing streptococcal pharyngitis and also an alternative to antibiotic prophylaxis for the prevention of rheumatic fever recurrences. Acute S. pyogenes infections and their non-suppurative sequelae continue to exact a severe toll on susceptible populations. Prior to the development of BLIS K12 the only available strategy has been treatment of the acute streptococcal infections as they occur by administration of therapeutic doses of a broad-spectrum antibiotic such as penicillin.
Studies have shown that the taking of lozenges containing BLIS K12 by children and adults can effect a reduction in the occurrence of streptococcal pharyngitis. Otitis media-prone infants given a paediatric formulation of BLIS K12 for two weeks prior to ventilation tube placement displayed colonisation of the adenoid tissue and more recently the taking of BLIS K12 was found to reduce the occurrence of secretory otitis media in children. A relative deficiency of S. salivarius in the oral cavity has been linked to the overgrowth of malodorous bacteria on the tongue and the development of bad breath (halitosis).
The more recently developed probiotic S. salivarius strain M18 (BLIS M18) differs from BLIS K12 in having additional BLIS activity against the mutans streptococci, bacteria that are commonly implicated in the development of dental caries. BLIS M18 also produces strong dextranase activity. Successful colonisation of young schoolchildren with BLIS M18 has been shown to reduce both the levels of mutans streptococci and the plaque index.
Professor Tagg continues his work with Blis Technologies in our Dunedin laboratory. He has isolated more than 2000 strains of bacteria during the course of his study and research, and his role now is to continue looking at how those strains can be used to the benefit of human health.