The journal Science unveiled a groundbreaking study titled Base-modified nucleotides mediate immune signaling in bacteria, spearheaded by Professor Han Wenyuan's team at Huazhong Agricultural University on Feb 21.

The team unearthed a novel bacterial defense mechanism utilizing base-modified nucleotides as secondary messengers, aptly christened the "Kongming".

Upon phage invasion, the unsuspecting deoxynucleotide kinase (DNK) within the phage becomes the pivotal "switch" triggering bacterial immune response: KomA seizes control of DNK, transforming deoxyadenosine monophosphate (dAMP) into the specialized signaling molecule deoxyinosine 5'-triphosphate (dITP). This unique molecule activates the KomC protein, leading to the degradation of the essential intracellular substance NAD⁺, effectively incapacitating the phage's replication due to "energy depletion". This intricate system cleverly leverages enzymes encoded by the invaders for defense, echoing the strategic brilliance of Zhuge Liang's tale Borrowing Arrows with Thatched Boats. Zhuge Liang, a renowned statesman and military strategist during the Three Kingdoms period (220-280), was known by his courtesy name Kongming.

The immune mechanism of the Kongming signaling pathway (left) and the immune evasion mechanism of bacteriophages (right). [Photo/news.hzau.edu.cn]

In a compelling tale of microbial warfare, phages have evolved countermeasures to combat the bacterial "onslaught". This evolutionary arms race, akin to a dance of spear and shield, sheds light on the competitive dynamics of nucleotide metabolism within the microbial realm.

This seminal study not only unveils the pivotal role of atypical nucleotides as signaling molecules in bacterial immunity but also shatters the conventional framework of immune signaling pathways. It sets the stage for the development of innovative research paradigms and further investigations into the physiological functions of atypical nucleotides across diverse species.