Loss of plasmid DNA coding for beta-lactamase during experimental infection with Haemophilus influenzae type b.

Apparent R factor-negative segregation was documented during infection of infant monkeys with two of three strains of ampicillin-resistant Haemophilus influenzae type b. In vitro the bacterial population of one strain (A-Sm) uniformly produced beta-lactamase. All bacteria isolated from blood or cerebrospinal fluid from both animals inoculated with strain A-Sm produced the enzyme. In contrast, 98% and 96% of bacteria from two other strains produced beta-lactamase in vitro. After intranasal inoculation of infant Macacca mulatta with these two strains, bacteria isolated from blood and cerebrospinal fluid uniformly did not produce beta-lactamase. Loss of the beta-lactamase-producing phenotype was associated with loss of plasmid DNA. Strains containing a mixed population of bacteria may undergo spontaneous loss of plasmid DNA during experimental infection. It is suggested that in these strains the bacteria carrying plasmids are less virulent.