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Acquisition of certain streptomycin-resistant (str) mutations enhances antibiotic production in bacteria.

ABSTRACT: Physiological differentiation (including antibiotic production) in microorganisms usually starts when cells encounter adverse environmental conditions and is frequently accompanied by an increase in the accumulation of intracellular ppGpp. We have found that the acquisition of certain streptomycin-resistant (str) mutations enables cells to overproduce antibiotics, demonstrating an increase in productivity 5- to 50-fold greater than that of wild-type strains. The frequency of such antibiotic-overproducing strains among the str mutants was shown to range from 3 to 46%, as examined with several strains of the genera Streptomyces, Bacillus, and Pseudomonas. Analysis of str mutants from Bacillus subtilis Marburg 168 revealed that a point mutation occurred within the rpsL gene, which encodes the ribosomal protein S12, changing Lys-56 (corresponding to Lys-43 in Escherichia coli) to Asn, Arg, Thr, or Gln. Antibiotic productivity increased in a hierarchical manner depending upon which amino acid residue replaced Lys at this position. The strA1 mutation, a genetic marker frequently used for mapping, had no effect on antibiotic productivity even though it was found to result in an amino acid alteration of Lys-56 to Ile. Gene replacement experiments with the str alleles demonstrated unambiguously that the str mutation is responsible for the antibiotic overproductivity observed. These results offer a rational approach for improving the production of antibiotic (secondary metabolism) from microorganisms.

SUBMITTER: Hosoya Y

PROVIDER: S-EPMC105730 | biostudies-literature | 1998 Aug

REPOSITORIES: biostudies-literature

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Acquisition of certain streptomycin-resistant (str) mutations enhances antibiotic production in bacteria.

Hosoya Y Y Okamoto S S Muramatsu H H Ochi K K

Antimicrobial agents and chemotherapy 19980801 8

Physiological differentiation (including antibiotic production) in microorganisms usually starts when cells encounter adverse environmental conditions and is frequently accompanied by an increase in the accumulation of intracellular ppGpp. We have found that the acquisition of certain streptomycin-resistant (str) mutations enables cells to overproduce antibiotics, demonstrating an increase in productivity 5- to 50-fold greater than that of wild-type strains. The frequency of such antibiotic-over ...[more]

PMID: 9687404

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Project description:Antibiotic-resistant bacteria are associated with increased patient morbidity and mortality. It is unknown whether wearing gloves and gowns for all patient contact in the intensive care unit (ICU) decreases acquisition of antibiotic-resistant bacteria.To assess whether wearing gloves and gowns for all patient contact in the ICU decreases acquisition of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) compared with usual care.Cluster-randomized trial in 20 medical and surgical ICUs in 20 US hospitals from January 4, 2012, to October 4, 2012.In the intervention ICUs, all health care workers were required to wear gloves and gowns for all patient contact and when entering any patient room.The primary outcome was acquisition of MRSA or VRE based on surveillance cultures collected on admission and discharge from the ICU. Secondary outcomes included individual VRE acquisition, MRSA acquisition, frequency of health care worker visits, hand hygiene compliance, health care–associated infections, and adverse events.From the 26,180 patients included, 92,241 swabs were collected for the primary outcome. Intervention ICUs had a decrease in the primary outcome of MRSA or VRE from 21.35 acquisitions per 1000 patient-days (95% CI, 17.57 to 25.94) in the baseline period to 16.91 acquisitions per 1000 patient-days (95% CI, 14.09 to 20.28) in the study period, whereas control ICUs had a decrease in MRSA or VRE from 19.02 acquisitions per 1000 patient-days (95% CI, 14.20 to 25.49) in the baseline period to 16.29 acquisitions per 1000 patient-days (95% CI, 13.48 to 19.68) in the study period, a difference in changes that was not statistically significant (difference, ?1.71 acquisitions per 1000 person-days, 95% CI, ?6.15 to 2.73; P?=?.57). For key secondary outcomes, there was no difference in VRE acquisition with the intervention (difference,??0.89 acquisitions per 1000 person-days; 95% CI, ?4.27 to 6.04, P?=?.70), whereas for MRSA, there were fewer acquisitions with the intervention (difference,??2.98 acquisitions per 1000 person-days; 95% CI, ?5.58 to ?0.38; P?=?.046). Universal glove and gown use also decreased health care worker room entry (4.28 vs 5.24 entries per hour, difference, ?0.96; 95% CI, ?1.71 to ?0.21, P?=?.02), increased room-exit hand hygiene compliance (78.3% vs 62.9%, difference,?15.4%; 95% CI, 8.99% to 21.8%; P?=?.02) and had no statistically significant effect on rates of adverse events (58.7 events per 1000 patient days vs 74.4 events per 1000 patient days; difference,??15.7; 95% CI, ?40.7 to 9.2, P?=?.24).The use of gloves and gowns for all patient contact compared with usual care among patients in medical and surgical ICUs did not result in a difference in the primary outcome of acquisition of MRSA or VRE. Although there was a lower risk of MRSA acquisition alone and no difference in adverse events, these secondary outcomes require replication before reaching definitive conclusions.clinicaltrials.gov Identifier: NCT0131821.

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Acquisition of certain streptomycin-resistant (str) mutations enhances antibiotic production in bacteria.

Publications

Acquisition of certain streptomycin-resistant (str) mutations enhances antibiotic production in bacteria.

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