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.
Trzcinski
Krzysztof
K
Department of Epidemiology and Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA. ktrzcins@hsph.harvard.edu
Thompson
Claudette M
CM
Gilbey
Andrea M
AM
Dowson
Christopher G
CG
Lipsitch
Marc
M
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