Incremental increase in fitness cost with increased beta -lactam resistance in pneumococci evaluated by competition in an infant rat nasal colonization model.
BACKGROUND
We evaluated the impact of resistant penicillin-binding protein (PBP) allele acquisition on the ability of penicillin-resistant (PEN-R) pneumococcal strains to compete with penicillin-susceptible (PEN-S) ancestors for upper-respiratory-tract (URT) colonization.


METHODS
PEN-S serotype 2, 6B, and 9V strains were transformed into derivatives expressing an increasing number of PEN-R PBP forms (2X, 2X-1A, and 2X-1A-2B for serotype 2 and 2X, 2X-2B, and 2X-2B-1A for 6B and 9V). Infant rats were inoculated intranasally with a mix of a PEN-R and PEN-S strains. For consecutive days, samples were collected for assessment of the ratio of PEN-S to PEN-R cells colonizing the URT. The selective index (SI), defined as the change in the natural logarithm of the ratio of PEN-S to PEN-R strains from the inoculum to the nasal-wash samples, quantified differences in fitness.


RESULTS
SIs significantly > 0 (indicating a cost of resistant allele acquisition) were observed 4-5 days after colonization in all but serotype 6B pbp2x transfomants. Additional replacements with low-affinity forms of pbp2b and pbp1a genes reduced further ability to compete in all strains.


CONCLUSIONS
The cost of penicillin-resistance acquisition for the Streptococcus pneumoniae strain competing with its susceptible ancestor to colonize the URT increases with the number of resistant pbp alleles acquired.
Department of Epidemiology and Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA. ktrzcins@hsph.harvard.edu
Krzysztof
K
Trzcinski
Claudette M
CM
Thompson
Andrea M
AM
Gilbey
Christopher G
CG
Dowson
Marc
M
Lipsitch
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D005798:Genes, Bacterial; D008969:Molecular Sequence Data; D009305:Nasopharynx / Q000382:microbiology*; D010403:Penicillin Resistance / Q000235:genetics*; D046915:Penicillin-Binding Proteins / Q000235:genetics*; D010406:Penicillins / Q000494:pharmacology; D010641:Phenotype; D011008:Pneumococcal Infections / Q000382:microbiology*; D051381:Rats; D013296:Streptococcus pneumoniae / Q000166:cytology / Q000187:drug effects* / Q000235:genetics*
D046915:Penicillin-Binding Proteins; D010406:Penicillins