Early impressions concerning actinomycetal infections that may play a role in the pathogenesis of eosinophilia-myalgia syndrome (EMS) and other ‘new illnesses’

Abstract

Actinomycetal infections by Actinomyces, Nocardia, and Streptomyces appear to be increasing in incidence. Clinical and laboratory data from twelve patients believed to have subclinical actinomycete-streptomycete infections (ASI) ∗ ∗ For this paper, the actinomycete-streptomycete combination is used because there are crossovers in the literature as to nomenclature. For example, Streptomyces fradiae is also referred to as Actinomyces fradiae. Generally it is the antibiotic producers (streptomycetes) that are the subject of this paper. are presented. It is proposed that the recent epidemic of eosinophilia-myalgia syndrome (EMS) may have been caused by pre-existing host ASI that generated toxic agents when individuals ingested supplemental l-tryptophan (LT). LT is the substrate used by streptomycetes to synthesize actinomycins, extremely cytotoxic metabolites that could have accounted for symptoms seen in EMS. Actinomycins inhibit CoA activity and interfere with the synthesis and utilization of amino acids. LT also provides streptomycetes with additional NAD, a substance of great importance to their DNA synthesis and metabolic activity. With increased activity, streptomycin, chloramphenicol, adriamycin or any one of the many secondary metabolites (antibiotics) produced by Streptomyces could be endogenously generated in greater quantities. The clinical result would be increased host toxicity. A contaminant that has been isolated from case associated lots of LT may have simply provided additional tryptophan for an ASI. It is also possible that a nucleotide or similar substance in the case associated LT products caused increased activation of tryptophan-2,3-dioxygenase, the rate-limiting enzyme required for the production of NAD and/or actinomycin. Potential reasons for ASI, atypical forms of actinomycete-streptomycete micro-organisms, and the possibility of involvement in other diseases are discussed.