When salt-tolerant Myxococcus cells are moved to a seawater environment, they change their growth, morphology, and developmental behavior. Outer membrane proteins and signal transduction pathways may play important roles in this shift. Chip hybridization targeting the genes predicted to encode 226 twocomponent signal transduction pathways and 74 outer membrane proteins of M. xanthus DK1622 revealed that the expression of 55 corresponding genes in the salt-tolerant strain M. fulvus HW-1 was significantly modified (most were downregulated) by the presence of seawater. Sequencing revealed that these seawater-regulated genes are highly homologous in both strains, suggesting that they have similar roles in the lifestyle of Myxococcus. Seven of the genes that had been reported in M. xanthus DK1622 are involved in different cellular processes, such as fruiting body development, sporulation, or motility. The outer membrane (Om) gene Om031 had the most significant change in expression (downregulated) in response to seawater, while the twocomponent system (Tc) gene Tc105 had the greatest increase in expression. Their homologues MXAN3106 and MXAN4042 were knocked out in DK1622 to analyze their functions in response to changes in salinity. In addition to having increased salt tolerance, sporulation of the MXAN3106 mutant was enhanced compared to that of DK1622, whereas mutating gene MXAN4042 produced contrary results. The results indicated that the genes that are involved in the cellular processes that are significantly changed in response to salinity may also be involved the salt tolerance of Myxococcus cells. Regulating the expression levels of these multifunctional genes may allow cells to quickly and efficiently respond to changing conditions in coastal environments.Isolation techniques based on the formation of fruiting body structures reveal that myxobacteria primarily inhabit various terrestrial environments (5, 20). Salt-tolerant fruiting myxobacterial strains from coastal environments can also be found if the enriching medium is prepared with diluted seawater (16). The salt-tolerant myxobacterial strains exhibit significant shifts in growth, development, and cellular behavior in response to the presence or absence of seawater. For example, when grown in medium with yeast cells as the only nutrient source, the salt-tolerant strain Myxococcus fulvus HW-1 requires a high cell concentration to initiate growth if the cells were collected from seawater-free cultures; the threshold number of cells required for growth decreases if the cells were from seawatercontaining cultures (31). On nutrient-deficient plates, salt-tolerant Myxococcus strains are able to develop typical fruiting bodies only when the seawater concentration is low or absent (the optimal seawater concentration for the development of fruiting bodies varies from 0% to 60% for different salt-tolerant Myxococcus strains) (27). Although the development process is inhibited by high concentrations of seawater, the myxospores can be developed directly from vegetat...