Off the wall

O ne of the most intriguing events in the history of life on earth is the evolution of self-replicating cells. Indeed, it is dazzling to even think about the complexity of the evolutionary changes required to go from a random mixture of molecules to highly organized bacterial cells that are capable of replicating themselves. A predominant theory is that RNA may have formed the basic genetic element in primordial cells and also catalysed reactions, only later to be followed by DNA and proteins (Gilbert, 1986; Orgel, 2004). Encapsulating these molecules inside a single structure would have been a key step towards creating life. However, many important questions are still a matter of debate. How did the primordial cells become encapsulated? How did these primitive life forms proliferate in the absence of proteins? And how did the molecular machinery needed for cell division emerge? Now, in eLife, Romain Mercier, Yoshikazu Kawai and Jeff Errington at the University of Newcastle show that in the absence of their cell wall, different classes of bacteria proliferate using common principles (Mercier et al., 2014). Such cells can proliferate without the molecular machinery that is usually needed for cell division and cell-wall synthesis (Figure 1), thereby providing insights into what ancient microbial life could have looked like. One of the defining structures of modern bacteria is their cell wall, which is predominantly composed of a polymer of sugars and amino acids called peptidoglycan (PG). It was demonstrated around 80 years ago that many bacteria can grow without a structural cell wall: these bacteria are called L-forms because they were first discovered in the Lister institute (Klieneberger, 1935). Classically, L-forms were isolated by cultivating cells in solutions containing high levels of chemicals that inhibit the synthesis of pepti-doglycan, and lytic enzymes that break down cell walls (Allan, 1991). However, the difficulties associated with this method have meant that a consensus regarding how L-forms grow and proliferate has so far remained elusive. Mercier, Kawai and Errington now show that common principles for L-form proliferation exist in Gram-positive and Gram-negative bacteria. Previous work focused on the Gram-positive Bacillus subtilis (Mercier et al., 2013); now they have now generated L-forms in the Gram-positive bacteria Staphylococcus aureus and Corynebacterium glutamicum, as well as in the Gram-negative Escherichia coli. L-form growth could be readily realised in these bacteria by using antibiotics that specifically block early steps in cell-wall precursor synthesis (Mercier et …