EPIDERMAL GROWTH FACTOR-BINDING PROTEIN IN MYCOBACTERIUM-AVIUM AND MYCOBACTERIUM-TUBERCULOSIS - A POSSIBLE ROLE IN THE MECHANISM OF INFECTION

Epidermal growth factor (EGF) is a potent mitogen for a variety of euk aryotic cells, EGF is found in a number of tissues and is prevalent in necrotic tissues and granulomata. The biological effect of EGF on mam malian cells is initiated by the binding to a specific receptor. Both Mycobacterium avium and Mycobacterium tuberculosis cause lung infectio ns and localized or disseminated disease in both patients without AIDS and those with AIDS. Histopathologic studies show necrosis in the lun g, liver, and splenic tissues of patients with disseminated mycobacter ial infection. In the course of experiments to examine the effect of g rowth factors on macrophages, it was observed that M. avium and M. tub erculosis but not Mycobacterium smegmatis cultured in the presence of 5, 50, or 500 ng of EGF per ml grew significantly faster than mycobact eria cultured in the absence of EGF. I-125-EGF was found to bind to M. avium and M. tuberculosis, and the binding was competitively inhibite d by unlabeled EGF. A receptor for EGF was identified on mycobacteria. Incubation of mycobacteria with EGF prior to infection of macrophage monolayers resulted in faster bacterial growth within macrophages comp ared with that of mycobacteria not incubated with EGF. EGF-binding pro tein was cloned and expressed in Escherichia coli, and subsequently th e protein was purified and the N-terminal amino acids were sequenced. These results suggest that EGF is a growth factor for pathogenic mycob acteria in granulomatous tissues and within macrophages and might enha nce growth rates of both intracellular and extracellular mycobacteria in the site of infection.