Mycoplasma suis, a member of the hemotrophic mycoplasma (HM) group, parasitize erythrocytes of pigs. Increasing evidence suggests that M. suis is also a zoonotic agent. Highly pathogenic strains of M. suis (e.g., M. suis KI3806) have been demonstrated to invade erythrocytes. This complete sequenced and manually annotated genome of M. suis KI3806 is the first available from this species and from the HM group. The DNA was isolated from blood samples of experimentally infected pigs due to the lack of an in vitro cultivation system. The small circular chromosome of 709,270 bp, encoding an unexpectedly high number of hypothetical proteins and limited transport and metabolic capacities, could reflect the unique lifestyle of HM on the surface of erythrocytes.Hemotrophic mycoplasmas (HM) are epierythrocytic, wallless bacteria that comprise a single phylogenetic cluster within the genus Mycoplasma (5). HM infections are found in a wide range of animals (e.g., Mycoplasma suis in pigs), causing infectious anemia (3, 4). The unique life cycle of M. suis and other HM on erythrocytes implies special features allowing HM to adhere to erythrocytes or to perform metabolic exchanges. Moreover, M. suis can invade erythrocytes, leading to high virulence and resistance to antibiotics (2). So far, HM cultivation in cell-free medium has failed, indicating that HM have a special metabolism and/or a high adaption to their hosts.We determined the genome of M. suis strain KI3806, a highly pathogenic and invasive strain. DNA was isolated from experimentally infected piglets using pulsed-field gel electrophoresis and sequenced (EurofinsMedigenomix; Germany) (1, 2).The circular chromosome of M. suis KI3806 is composed of 709,270 bp with a 31%-GC content. The genome includes 32 tRNAs and a single-copy 16S rRNA which is separated from the 23S and 5S rRNA by ϳ165 kb and encoded on the opposite strand. The predicted 809 open reading frames (ORFs) comprise a density of 1.119 genes per kilobase. The average protein size is 259 amino acids, with a coding percentage of 87%. The low number of estimated paralogs (36 coding determining regions [CDS]; 70% identity) corresponds to only one putative transposase. The genome differs from other mycoplasma genomes in the high portion of predicted proteins without functional assignment (64.6%; 523/809), which may reflect the adaptation of M. suis to a special environment but could also be a result of large integration events due to the unit-like organization of these proteins (RG1_33888.0.50303 [region_position], RG2_77345.0.182976, RG3_214881.0.233523, RG4_416009.0.454949, RG5_ 456815.0.523918, and RG6_581193.0.614049). These six regions encode 19 proteins of unknown function per unit at least and sum up to ϳ280 kb, which does not include housekeeping genes but does include sequences for 413 unassigned proteins. A similar scenario is known for the integrative conjugative elements (ICEs) from Mycoplasma agalactiae (6), but ICEs show different genetic content. In M. suis some phage-related proteins, i.e., an in...