The pathogenicity and prevalence of Mycoplasma penetrans, a Mycoplasma spec
ies recently isolated from humans, are still debated. A major P35 antigen,
which is used as target epitope in serological assays, was shown to be a ph
ase-variable lipid-associated membrane protein (LAMP). In this study, we pe
rformed a comparative analysis of the LAMP patterns from five M. penetrans
clinical isolates and from the type strain. Sodium dodecyl sulfate-polyacry
lamide gel electrophoresis profiles and immunoblots with sera serially coll
ected from an M. penetrans-infected patient indicated that these strains ex
pressed different LAMP repertoires. Furthermore, the intraclonal variation
in the expression of LAMPS (P34A, P34B, P35, and P38) was monitored by immu
noblot analysis with three specific monoclonal antibodies (MAbs) developed
in this study and MAb 7 to P35. The phase variation of these LAMPS occurs i
n an independent manner, with frequencies of variation ranging from 10(-2)
to 10(-4) per cell per generation. Consistent with their amphipathic nature
, the P34B and P38 antigens were found exposed at the cell surface. The DNA
sequence encoding the P38 antigen was defined and found to be related to t
hose of the P35 gene and other putative LAMP-encoding genes, suggesting tha
t these variable antigens are encoded by a family of related genes. Finally
, the serum samples from an M. penetrans-infected patient contained antibod
ies that reacted with a P36 antigen expressed in different M. penetrans str
ains but not in the isolate recovered from this patient. This result sugges
ted that in vivo phase variation of P36 occurred, which would support a rol
e for these LAMP variations in avoiding the host's immune vigilance.