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NATURE, FORMATION, AND ACTIVITIES 



populations which are made streptomyc-in- 

 resistant by DXA deri\'ed from strepto- 

 mycin-resistant H. parainfluenzae and vice 

 versa has been increased 4- to b")-t'old l)y the 

 replication of the heterologous species 

 streptomycin-resistant DNA in the heterolo- 

 gous species. An alteration of the heterolo- 

 gous DNA by the host was suggested. 



Lightl)Own (1957) made a study of the 

 development of resistance to streptomycin 

 by Ps. pyocyaneus. Resistance was found not 

 to be enzymatic, but to be due to the produc- 

 tion of alkyl-substituted quinoline-X-oxides, 

 which are potent inhibitors of bacterial cyto- 

 chrome electron transport at concentrations 

 that give increased resistance to strepto- 

 mycin for organisms such as B. subtilis and 

 Staph, aureus. Resistance to streptomycin 

 was believed to depend on the de\'elopment 

 and choice of alternati^'e pathways of metab- 

 olism; the effects of the ([uinoline-X-oxides 

 may be due to the inhibition of the Pasteur 

 effect, allowing more active glycolysis to 

 occur aerobically. Obligate aerobes were 

 believed to possess an alternative to the 

 cytochrome terminal pathway. This ma}^ 

 be, in part, a flavoprotein oxidase-peroxidase 

 path. Certain elements, notably Mg, accel- 

 erate the development of resistance to 

 streptomycin; others, hke Co, have an 

 inhibitory effect (Chernomordik and Kobe- 

 leva, 1959). 



Pollak (195()) studied antibiotic resistance 

 of M. kansasii, an atypical acid-fast organ- 

 ism previously known as the "yellow bacil- 

 lus." It was as susceptible to streptomycin as 

 M. tuberculosis, but about 5 to 10 times as 

 resistant to /^-aminosalicylic acid and isonia- 

 zid. 



Sebek (1958) investigated growth-inhibi- 

 tory effects of neomycin B, neomycin C, and 

 neamine on 24 bacterial species (Table 33). 

 Particularly striking differences were ob- 

 tained in Corynebacierium sp. and Sarcina 

 lutea. The growth of the first was inhibited 

 by about 250 /xg per ml of neamine or neo- 



mycin C but by only 0.4 to 1.6 /xg per ml of 

 neomycin B. When neomycin C and neamine 

 were added in \-arying ratios and in different 

 combinations to neomycin B, the inhibitory 

 concentrations of neomycin B remained 

 virtually unchanged. The organism readily 

 acciuired resistance and cross-resistance to a 

 high degree to neamine and neomycin C but 

 only slightly to neomycin B. It was suggested 

 that the diaminohexose portion of neomycin 

 B is responsible for the specific growth- 

 inhibitory effect of this antibiotic on these 

 two bacteria. Cross-resistance between strep- 

 tomycin and neomycin has been studied by 

 Sidi et al. (1958). 



Several cross-resistant groups are now 

 recognized among the antibiotics of actino- 

 mycetes: (1) streptomycin, streptothricin, 

 viomycin, and neomycin, as well as kana- 

 mycin, catenulin, and paromomycin; (2) the 

 tetracyclines, chloramphenicol, and possibly 

 penicillin; (3) erythromycin, carbom^'cin, 

 celesticetin, oleandomycin, and spiramycin. 



Kunin et al. (1958) observed that kana- 

 mycin, paromomycin, and neomycin had 

 essentially the same activity against strains 

 of Staph, aureus and of various Enterobac- 

 teriaceae. Bacteria made resistant to any 

 one of these three antibiotics by subcultures 

 on that antibiotic also exhibited complete 

 cross-resistance to the other two. Freshly 

 isolated cultures did not show significant 

 cross-resistance between streptomycin and 

 these three antibiotics; however, sti'ains 

 made resistant to any one of the three also 

 showed increases in resistance to strepto- 

 mycin; strains made resistant to the latter 

 exhibited only minor increases in resistance 

 to the others. Cultures of staphylococci 

 comprising i)oth parent and resistant (to all 

 four antibiotics) variants were of the same 

 phage type; resistant variants of Kl. pneu- 

 moniae and E. coli, however, retained their 

 serological specificity. During oral treatment 

 with paromomycin or kanamycin, fecal 

 organisms were resistant to the antibiotic 



