Studies on the Virulence of Tubercle Bacilli

Abstract

It has been reported (1) that a petroleum ether-soluble material can be extracted from virulent tubercle bacilli. Since it was obtained only from "cordforming" organisms (2) it was called "cord factor." Mter being subjected to extraction with petroleum ether, the bacteria were still able to grow normally in suitable culture media. This fact suggested that the cord factor was located at the surface of the bacterial cell and that its removal did not disturb any essential structures of the cell. On the other hand, the importance of the bacterial surface in the establishment of an infection was emphasized by the fact that the isolated cord factor exerts some of the effects of intact virulent organisms, while the behavior of virulent bacteria after removal of the cord factor was in some respects more characteristic of avirulent than of virulent organisms. It is noteworthy that young cultures yielded considerably more cord factor than older ones.These findings were consistent with the previous work of Middlebrook, Dubos, and Pierce (2) calling attention to the cord formation by virulent tubercle bacilli and correlating this phenomenon with properties of the bacterial surface concerned in the virulence of tubercle bacilli. Further evidence for differences in the surface structure of virulent and non-virulent mycobacteria was brought out in another series of experiments (3). Virulent organisms were shown to be considerably less permeable to the dye methylene blue than noncord-forming avirulent bacteria. Mter extraction with petroleum ether, however, they became equally permeable. Apparently the petroleum ether extracts a surface material which is responsible for the low permeability of virulent strains of tubercle bacilli to even small molecules like methylene blue. Moreover, when cord-forming cultures were allowed to age in vitro, the ceils became increasingly permeable to methylene blue; the greater the virulence of a strain, the longer its organisms remained relatively impermeable to the dye.This observation parallels the small yield of cord factor obtained from older cultures, on one hand, and the fact that avirulent bacteria which did not contain any measurable amount of cord factor were completely permeable to methylene blue, on the other.Our earlier observations had already suggested that the cord factor was in some way concerned in the virulence of tubercle bacilli. If this was true, young cultures possessing more cord factor, should also be more virulent for susceptible animals than older cultures of the same strain.The experiments reported in the present paper seem to bear out this working hypothesis. Materials and MethodsBacteria.--Three strains of tubercle bacilli were used in these experiments: The human strain H37Rv, obtained from the collection of Dr. R..L Dubos; a human strain Jamaica No. 22, received from Dr. J. Freund; and a bovine strain Vall~e, originally obtained from the Pasteur Institute in Paris and propagated on egg media for at least 20 years at the Institute for Hygiene of the Universtiy of Ba...

Mycobacterial glycolipid trehalose 6,6′-dimycolate-induced hypersensitive granulomas: contribution of CD4+ lymphocytes

“…They constitute more than 50 % of the dry weight of the organism and have been implicated as potential virulence factors (Kolattukudy et al, 1997). More than a half a century ago, Hubert Bloch identified cord factor as a 'toxic substance' that when extracted from virulent organisms caused them to lose their virulence (Bloch, 1950), and when added during infection exacerbated disease (Bloch & Noll, 1955). This substance was later identified as the mycobacterial glycolipid trehalose 6,69-dimycolate or TDM (Noll et al, 1956).…”

CD3+ cells transfer the hypersensitive granulomatous response to mycobacterial glycolipid trehalose 6,6′-dimycolate in mice

“…In the early 1950s, Bloch identified a toxic lipid he termed 'cord factor' (later revealed to be TDM), which, when extracted from the surface of virulent mycobacteria, converted them to an avirulent form (Bloch, 1950;Noll et al, 1956). Since then, there has been much controversy over the role of TDM in organism virulence (Hunter et al, 2006).…”

“…However, recent findings suggest that the pathophysiological response to TDM manifests itself in multiple ways. TDM involvement in toxicity, inhibition of phagosomal maturation, and primary and hypersensitive granulomatous responses is only now being fully appreciated (Bloch, 1950;Guidry et al, 2004;Hunter et al, 2006;Indrigo et al, 2002;Lima et al, 2001;Seggev et al, 1984;Spargo et al, 1991;Yamagami et al, 2001;Yarkoni & Rapp, 1978). The lipid-rich cell walls of mycobacteria have proven to be an important defence mechanism aiding their survival within the host.…”

Studies on Tubercle Bacillus-Monocyte Relationship

“…Bloch (17,18) has reported on the ability of "cord factor" to inhibit the migration of leucocytes in tissue cultures and on its lethality for mice. Spitznagel and Dubos (19) have shown that a toxic fraction soluble in monochlorobenzene and insoluble in cold petroleum ether may be extracted from tubercle bacilli.…”