Nitrogen-fixing rhizobial bacteria and leguminous plants have evolved complex signal exchange mechanisms that allow a specific bacterial species to induce its host plant to form invasion structures through which the bacteria can enter the plant root. Once the bacteria have been endocytosed within a host-membrane-bound compartment by root cells, the bacteria differentiate into a new form that can convert atmospheric nitrogen into ammonia. Bacterial differentiation and nitrogen fixation are dependent on the microaerobic environment and other support factors provided by the plant. In return, the plant receives nitrogen from the bacteria, which allows it to grow in the absence of an external nitrogen source. Here, we review recent discoveries about the mutual recognition process that allows the model rhizobial symbiont Sinorhizobium meliloti to invade and differentiate inside its host plant alfalfa (Medicago sativa) and the model host plant barrel medic (Medicago truncatula).The recent completion of the Sinorhizobium meliloti genome sequence, and the progress towards the completion of the Medicago truncatula genome sequence, have led to a surge in the molecular characterization of the determinants that are involved in the development of the symbiosis between rhizobial bacteria and leguminous plants. Aromatic compounds from legumes called flavonoids first signal the rhizobial bacteria to produce lipochitooligosaccharide compounds called Nod factors 1 . Nod factors that are secreted by the bacteria activate multiple responses in the host plant that prepare the plant to receive the invading bacteria. Nod factors and symbiotic exopolysaccharides induce the plant to form infection threads, which are thin tubules filled with bacteria that penetrate into the plant cortical tissue and deliver the bacteria to their target cells. Plant cells in the inner cortex internalize the invading bacteria in host-membrane-bound compartments that mature into structures known Correspondence to G.C.W. gwalker@mit.edu. Competing interests statementThe authors declare no competing financial interests. DATABASES Invasion of plant rootsAlthough plant roots are exposed to various micro-organisms in the soil, their cell walls form a strong protective barrier against most harmful species. The early steps in the invasion of barrel medic (M. truncatula) and alfalfa (Medicago sativa) roots by S. meliloti are characterized by the reciprocal exchange of signals that allow the bacteria to use the plant root hair cells as a means of entry. Initial signal exchangeFlavonoid compounds (2-phenyl-1,4-benzopyrone derivatives) produced by leguminous plants are the first signals to be exchanged by host-rhizobial symbiont pairs 1 (FIG. 1). Flavonoids bind bacterial NodD proteins, which are members of the LysR family of transcriptional regulators, and activate these proteins to induce the transcription of rhizobial genes 1,2 . For example, the M. sativa-derived flavonoid luteolin stimulates binding of an active form of NodD1 to an S. meliloti 'nod-box' p...

Rhizobial bacteria colonize legume roots for the purpose of biological nitrogen fixation. A complex series of events, coordinated by host and bacterial signal molecules, underlie the development of this symbiotic interaction. Rhizobia elicit de novo formation of a novel root organ within which they establish a chronic intracellular infection. Legumes permit rhizobia to invade these root tissues while exerting control over the infection process. Once rhizobia gain intracellular access to their host, legumes also strongly influence the process of bacterial differentiation that is required for nitrogen fixation. Even so, symbiotic rhizobia play an active role in promoting their goal of host invasion and chronic persistence by producing a variety of signal molecules that elicit changes in host gene expression. In particular, rhizobia appear to advocate for their access to the host by producing a variety of signal molecules capable of suppressing a general pathogen defense response.

To characterize the functions of MLL fusion transcripts, we cloned the gene that fuses to MLL in the translocation t(11;19)(q23;p13

BacA is an inner membrane protein associated with maintenance of chronic infections in several diverse host-pathogen interactions. To understand the function of the bacA gene in Mycobacterium tuberculosis (Rv1819c), we insertionally inactivated this gene and analyzed the resulting mutant for a variety of phenotypes. BacA deficiency in M. tuberculosis did not affect sensitivity to detergents, acidic pH, and zinc, indicating that there was no global compromise in membrane integrity, and a comprehensive evaluation of the major lipid constituents of the cell envelope failed to reveal any significant differences. Infection of mice with this mutant revealed no impact on establishment of infection but a profound effect on maintenance of extended chronic infection and ultimate outcome. As in alphaproteobacteria, deletion of BacA in M. tuberculosis led to increased bleomycin resistance, and heterologous expression of the M. tuberculosis BacA homolog in Escherichia coli conferred sensitivity to antimicrobial peptides. These results suggest a striking conservation of function for BacA-related proteins in transport of a critical molecule that determines the outcome of the host-pathogen interaction.

SummaryRhizobium sp. NGR234 nodulates many plants, some of which react to proteins secreted via a type three secretion system (T3SS) in a positive-( Flemingia congesta , Tephrosia vogelii ) or negative-( Crotalaria juncea , Pachyrhizus tuberosus ) manner. T3SSs are devices that Gram-negative bacteria use to inject effector proteins into the cytoplasm of eukaryotic cells. The only two rhizobial T3SS effector proteins characterized to date are NopL and NopP of NGR234. NopL can be phosphorylated by plant kinases and we show this to be true for NopP as well. Mutation of nopP leads to a dramatic reduction in nodule numbers on F. congesta and T. vogelii . Concomitant mutation of nopL and nopP further diminishes nodulation capacity to levels that, on T. vogelii , are lower than those produced by the T3SS null mutant NGR W W W W rhcN . We also show that the T3SS of NGR234 secretes at least one additional effector, which remains to be identified. In other words, NGR234 secretes a cocktail of effectors, some of which have positive effects on nodulation of certain plants while others are perceived negatively and block nodulation. NopL and NopP are two components of this mix that extend the ability of NGR234 to nodulate certain legumes.