untitled

natural biocontrol in field conditions, a classic ex-

ample being the role of fluorescent pseudomonads

(P. fluorescens and P. putida) in suppressing the take-all

disease of cereals.

Control of fungal infections of humans

The control of fungal infections of humans presents

considerable difficulties, because often the patient is

severely compromised or immunosuppressed (Chap-

ter 16). It is worth noting that even the common

antibacterial antibiotics such as penicillins and

cephalosporins do not work alone; they act in con-

junction with the host’s normal defenses. There are,

however, several antimycotic agents that can be used

successfully to treat human mycoses (Odds et al. 2003).

We consider these below.

Griseofulvin

Griseofulvin (Fig. 17.11) is a naturally occurring anti-

fungal antibiotic, produced by the fungus Penicillium

griseofulvum. It is insoluble in water but can be taken

orally in a microcrystalline form and it then accumu-

lates in the keratin precursor cells of the skin, nails, and

hair. It is used almost exclusively to control the der-

matophyte infections of the keratinized tissues, but it

is fungistatic rather than fungicidal, so for serious

infections the treatment must be prolonged until all

the infected tissues have been shed.

As noted earlier, griseofulvin causes growth distor-

tions of fungal hyphae in spore germination tests,

including thickening of the hyphal walls, associated with

heavy deposition of glucans. However, this is now

known to be a secondary effect, and the primary role

of griseofulvin is to interfere with the assembly of

microtubules or of the tubulin-associated proteins. It

causes abnormal nuclear division by disrupting the

spindle microtubules, and abnormal growth, presumably

by disrupting the microtubule-associated transport of

materials to the hyphal tip. In these respects, the role

of griseofulvin is similar to that of the benzimidazole

fungicides used for plant disease control, because

these also block microtubule assembly. But the benz-

imidazoles evidently act at a different site on micro-

tubules because mutants that develop resistance to

the benzimidazoles are not resistant to griseofulvin, and

vice versa.

Griseofulvin has been the main drug used to

treat dermatophyte infections for many years, and

although resistance to the antibiotic can occur quite

frequently in vitro, it has not been a major problem in

clinical practice. However, griseofulvin is now being pro-

gressively replaced by newer synthetic drugs, includ-

ing terbinafine and itraconazole, which are less toxic

and require shorter treatment times.

350 CHAPTER 17

No. of plants No. of dominant % of isolates with
Crop examined bacterial isolates antifungal properties

Sugarbeet 1550 6780 38
Maize 503 1508 27
Soybean 450 1139 21
Sunflower 450 1119 22
Barley 36 175 92
Grape 36 231 100

Table 17.4Bacteria with antifungal

properties isolated by “nonselective”

methods from the root zone of crop

plants. (Adapted from Leyns et al.

1990.)

Griseofulvin Terbinafine

CH 2 CH 2

N CH 3

CH 3 CH 3

H

CH 3

C

C

H

C C C

OCH 3 OCH 3

CI CH 3

O

O

CH 3 O O

Fig. 17.11Structures of griseofulvin and terbinafine, two compounds used to treat dermatophyte infections.