Jpn. J. Infect. Dis., 53, 2000

Laboratory and Epidemiology Commumications
Computer Simulation of SuⅣival of Mutants under Non‑Selective Condition

Yoshimitsd Yanaka, Ken‑Ichi Hanaki, Hiroshi Yoshikura and Kenji Yamamoto*Departmenl of Medical Ecology and lnformatics, International Medical Center ofJapan,

Toyama 1‑21‑I, Shinjuku‑ku, Tobo 162‑8655
Communicated by Hiroshi Ⅵ)shikura(Accepted November 22, 2000)

The horizontaltransmission of drug resistance PR) markers
from genetically modified foods (GMO) to intestinal bacteriaacquired DR from GMO‑derived food (though this event hasnot been unequivocally demonstrated) Canpersist in the over‑and their persistence are important issues in the recent

whelming number of resident bacteria in the intestines.

debate on the safetyof GMO‑derived food. This paper deals

The simulation was performed based on the followlng

with the latter question, i.e., whether bacteria which oncepremises. The bacterialflora consisted of a slngle species.

The replication rate was the same for the wild typeand the*Corresponding author: E‑mail: backen@ri.imcj.go.jp

mutant, and there was no selection advantage for either. The217Jpn. J. Infect. Dis., 53, 2000∩(I)∈]IudlnM+OLOquJnN

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Number of Divisions (t)Fig. I. Simulation of persistence of mutant.
C = 1,000, W(0) = 990, and m(0) = 10. Number ofsimulations was 50. The Tom and ToM values are indicated.

number of bacteria in the flora was constant. The above

premises were expressed by uslng the followlng four formulae:
W(t)+m(t)=W(0)+m(0)=C [1】,where w(t) and m(t) are numbers of wild type and mutant( OL)euOle≡C‑○JOqunN

bacteria at time t,W(t+1) = 2W(t) ‑ W.(t)【2],m(t+1) = 2m(t)一m.(t)【3],where.wr(t) and mr(t) are numbers of wild type or mutant

bacterla removed randomly from the flora (mechanically orby death) from time tto t+ 1, andw,(t)+m.(I)=C[4]as the total number of bacteria in the flora is constant.

The simulation was performed by uslng a Sun Ultra5 com‑puter (Micro Sun, Ltd., Palo Alto, Calif., USA)and C language.
Figure 1 shows 50 simulations performed for a condition
inwhich C = 1000, W(0) = 990, andm(0)= 10. The time in0200

400

600

800

1000

1200

which complete dis叩pearanCe Of the mutant occumd, i.e., I

TotAI Numbor of BActerJa (C)for m(t) = 0, was called complete disappearance time. To･ To

was variable from one simulation to another. In one slmula‑Fig. 2. Relation between size offlora and I.mand ToM values. Numbertion, the mutant did not disappear even a鮎r 452 divisions.

ofsimulations was 100.

The mean ofで｡ values was expressed by T｡m, and the maxi‑mumで｡ va)ue by TOM (as expected, this value will increase

with the trial number). Figure 2 shows the relation between

Though we used a computer in this report, We can probably

C and I?m (closed triangles) and that between C and ToM

solve the problem analytically, because the curves in Fig. 1(open trlangles) in the condition where only one mutant

suggest that血e problem can be reduced to a model orrandombacteria appeared in the nora, i.e., W(0) = C ‑ 1 and m(0) = 1.

walkwith one outlet. We can make a similar computation for

Examined C values were 100, 300, 600, 800, and 1,000, anda s血ation where mutants come up one a鮎r another or f♭r anumber of trials was 100.

situation where the species in question competes with other

The followlng Observations were made.

species.

Because the problem is simple, the above prediction can be(1) The mutant disappears in a finite length of time.

(2) T｡m is independent ofC.

checked experimentally by uslng a Chemostat with a device(3) TOM increaseswith C.

to keep the total number of bacteria constant.

When a mutant bacteria appears in aflora, it is eliminatedwithin a finite time. The mean ofで｡ values obtained from

This study was supported by the grants from the MimiS什ymultiple trials (tom) is constant irrespective of the size ofof Healthand Welfare of Japan, andthe Program for Promotion

the nora･ Howeyer, the longest time (ToM), among flora,ofFundamental Studies in Health Science for the Organiza‑

required for elimination of the mutant increases with the sizetion for Pharmaceutical Safetyand Research (OPSR), Japan.

of the nora.

218