The John Tagg Story

Professor Tagg’s first significant encounter with Streptococcus pyogenes – the bacteria that causes a 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.

Nevertheless, it just seemed to the young John Tagg that there must be a better way to defend against streptococcal sore throats.

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 lodgement 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 bacteriocidal 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. First John needed to familiarise himself with the idiosyncrasies of streptococcal behaviour and his conviction was that, in order to prevent S. pyogenes from assaulting its human host, it would be important to try to strengthen the territorial defensive capabilities of the non-virulent streptococcal component of our indigenous microbiota. It occurred to him that over the course of their lengthy co-evolution with humans it was the indigenous oral streptococcal populations that would surely have developed the most effective and specifically-targeted bacteriocin weaponry to counter competition for their space by rapidly-multiplying virulent streptococci.

John Tagg next undertook PhD research at Monash University – the theme of those studies being an exploration of the relationship between S. pyogenes infections and the induction of the autoimmune manifestations of rheumatic fever. He set about screening many hundreds of oral streptococci for their bacteriocin-producing capability (i.e. bacteriocinogenicity) and included amongst these streptococci was a series of S. pyogenes isolates from the Fairfield Infectious Diseases Hospital in Melbourne. On September 1, 1969, John discovered that number 22 in this series produced bacteriocin-like inhibitory activity against some other S. pyogenes strains when tested in a deferred antagonism assay. The inhibitory agent, later given the name streptococcin A-FF22, was the first of the streptococcal bacteriocins to be isolated and characterised.

Dr Lewis Wannamaker at the University of Minnesota was an influential leader in the field of streptococcal research and had played a major role in developing the original guidelines for the use of penicillin prophylaxis as a preventative against rheumatic fever recurrences. In 1972 Dr Wannamaker hosted a workshop on ‘Streptococci and Streptococcal Diseases’ at the University of Minnesota which was attended by many of the leading S. pyogenes researchers of that era. In his workshop summary, Dr Wannamaker remarked that “working with the streptococcus is like a love affair, which I guess explains why so many of us find it difficult to give up”. John Tagg could relate to this sentiment and wrote to him asking if they could work together, seeking a bacterial interference-based alternative to the use of penicillin for rheumatic fever prophylaxis

Three years of total streptococcal research immersion followed. Dr Wannamaker was generous in his support for John Tagg’s endeavours to find a harmless oral streptococcus capable of effectively engaging in bacteriocin-mediated warfare against S. pyogenes, while at the same time maintaining the view that what S. pyogenes really needed was greater scientific understanding – not extermination.

Before leaving Minnesota John Tagg wrote the first major review of the bacteriocins of gram-positive bacteria and upon purifying streptococcin A-FF22 demonstrated that it was closely similar to nisin, the best known and still the most widely applied of all the bacteriocins of gram-positive bacteria.

Rheumatic fever is a major public health concern in New Zealand, with a particularly high occurrence in the native Maori and Pacific Islander populations. In view of this John Tagg was excited in 1975 to obtain an academic position in the Microbiology Department at the University of Otago in Dunedin. His research agenda in New Zealand became firmly focused on finding a harmless oral streptococcal antagonist of S. pyogenes. He developed a procedure for the bacteriocin ‘fingerprinting’ of streptococci based on the deferred antagonism test in which a set of nine standard indicator bacteria are evaluated for their relative sensitivity to inhibitory substances released into an agar medium during the growth of a diametric streak culture of the test bacterium. It soon became clear that most (if not all) streptococci were probably capable of producing some sort of bacteriocin-like inhibitory activity.

The commercial outcome of these laboratory discoveries was the launching of the Dunedin-based company Blis Technologies Ltd in August 2000 and two years later the first oral probiotic product, BLIS K12™ ThroatGuard, appeared on the shelves of New Zealand pharmacies. A wide variety of BLIS K12™ products in powder, lozenge, chewing gum and ice cream formulations have subsequently been developed and many are now marketed internationally.

Professor Tagg continues his work with Blis Technologies in our Dunedin laboratory. He isolated more than 2000 strains of bacteria during the course of his study and research, and John’s role now is to continue looking at how those strains can be used to the benefit of human health.